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Celebrating 30 Years

As part of our 30th anniversary celebrations GEN asked leading tool providers for their thoughts on the key technologies that played the greatest role in driving the industry forward. We also wanted to learn what disruptive technologies they feel will have the greatest impact in the next 30 years.

Read on to see how they answered the following two questions:

Q1) Which specific technologies have had the greatest impact on the development of the life science industry over the past 30 years and why?

Q2) What biotechnologies do you think will be the most "disruptive" over the next 30 years and how will these techniques transform research, development, or manufacturing activities?

Dirk Löffert
Vice President Head of Sample & Assay Platform Technologies Global R&D

Q1 Answer:

Focusing on molecular technologies first, the introduction of pre-analytical tools for the isolation of DNA, RNA, and proteins has been extremely important as most assay technologies rely on highly purified, intact, and reproducibly obtained biomolecules from any source of biological starting material. The commercial market for a broad range of those pre-analytical tools for various starting materials and throughput formats has been created and shaped by QIAGEN. The core invention that revolutionized the life science industry has been the polymerase chain reaction (PCR) as it allowed for the first time to amplify nucleic acids to yield detectable amounts of DNA that can be easily further manipulated by other molecular techniques such as cloning and sequencing. Thus, PCR was not the starting point of recombinant molecular biology but an enormous facilitator that led to vast expansion of the life science market and dissemination of molecular techniques, shaping other life science-based industry sectors such as in vitro diagnostics. The most recent technology development, next-generation sequencing (NGS), combines the goods of array and sequencing technologies, providing massive parallel analysis of many nucleic acid molecules, effectively a genome, combined with the highest possible resolution of information obtained at the sequence level. Since NGS not only addresses whole genome sequencing but supports discovery in life sciences in many other applications such as targeted re-sequencing for variant analysis, gene expression analysis, and analysis of regulatory mechansims, e.g., in ChIPseq, it has become a kind of universal platform technology that will be indispensable for future discoveries in life sciences. Talking about cellular technologies, certainly FACS has become the dominating technology that allows the investigation of cells according to many different markers at the same time, eventually making discrete cells amenable to molecular analysis.

Q2 Answer:

Undoubtedly, next-generation sequencing is the current driver technology—however, given the dramatic changes through new molecular biology technologies during the last 30 years, it appears hardly possible to make predictions for more than a few years as the field changes so fast. The desire to analyze smaller biological entities may lead to further miniaturization and more sensitive methods that eventually may enable efficient analysis at the single-cell level, which may also be accompanied by new routes into imaging technologies. Another trend that will further fuel the field is personalized medicine, understanding the patient in the context of his individual biological background. New technologies will be needed that make this complex information easily and rapidly accessible. Thus, the life science sector may not be only driven by new molecular methods but also by novel bioinformatic tools for effective data analysis.

Gerd Haberhausen
Life Cycle Leader qPCR and Nucleic Acid Preparation
Roche Applied Science

Q1 Answer:

It was first and foremost the invention of the polymerase chain reaction (PCR) by Kary Mullis in 1983 that revolutionized molecular research and that was rewarded by the Nobel Prize in 1993. In the life science industry it was the enabling technology for all kinds of research studies. Finally, and with further inventions such as the use of dUTP and uracil N-glycosylase, PCR made its way into routine molecular diagnostics as well. Today's safety level in blood transfusion and modern viral monitoring wouldn't be possible without PCR.

Q2 Answer:

Today's next-gen sequencing technologies reveal a similar pattern like PCR in terms of market adoption and new rapid developments. While still in research, it will also make its way into routine diagnostics as it becomes more robust and convenient.

Frank Schacherert

Q1 Answer:

PCR, Sanger sequencing, NMR spectroscopy, and monoclonal antibodies all come to mind. They all provided fundamental tools to enable us to take a closer look at the molecules of life. Microarrays were the first pervasive high-throughput technology. Like with other industries, the internet and computerization have also had a dramatic impact. Without them, analysis of the resulting data would not have been possible.

Q2 Answer:

It seems to be a safe bet that next-generation sequencing will transform research and medicine. It is already now delivering new insights at an unprecedented rate, and it is a fundamentally applicable technology that can be used for understanding genomics as well as transcriptomics. Of course, the one thing certain about the future is that it will be different from what we think it will be.

Ali A. Javed, Ph.D
Director, R&D
Gene Link, Inc.

Q1 Answer:

Life science industry is more akin to incremental advances despite major breakthroughs; the last thirty years witnessed PCR and the rapid growth of amplification and probe-based technologies utilizing fluorescence detection instrumentation and computing. Genome-wide association studies (GWAS), polymorphism, and function prediction were all based on the ability to amplify genomic fragments utilizing probes and primers. Automated solid-phase oligonucleotide synthesis incremental advances facilitated quick and relatively inexpensive availability of primers and probes. It is this backbone technology that fueled advances in genomic studies.

Q2 Answer:

Disruptive technology seems too radical a term for life sciences as opposed to innovative and sustaining, but it is quite possible that certain technologies in combination have the potential to have major impact over the next thirty years. Life science research, in collaboration with physical sciences and computing, eventually will move toward the use of nanotechnology for most if not all instrumentation. I predict that current amplification and hybridization-based assays (due to detection sensitivities) will be replaced by assays based on direct detection of hybridization wavelength shift and/or fluorescence probes utilizing miniature laser spectrometers. Similarly, the immense volume of data gathered by GWAS will be used for virtual predictive expression profiles and management of clinical care to avoid drug contraindications. Gene therapy, a catch word for the last 50 years, has yet to benefit the population and possibly may come to fruition by the folks involved in tissue engineering.

Toni R. Hofhine
Gilson Knowledge Center Director
Gilson, Inc.

Q1 Answer:

Over the past thirty years, there have been many technologies with significant impact. The life science industry is quite large, and the past thirty years have showcased advancements in mass spectrometry for positive compound determination at significantly lower LODs and LOQs, in PCR and other PCR techniques for significantly advanced understanding of genes and general improvement on human health, in protein purification and peptide purification that further impact drug discovery, as well as the beginnings of structural genomics/proteomics for informational purposes on structure and function of proteins for future disease treatment. Adding automation to laboratories has been the number one factor in aiding these advancements—from electronic or motorized pipettes, to fully automated sample preparation and sample cleanup systems, to fully automated systems that aid natural product, drug synthesis, and protein synthesis purification. Competition within the R&D sector of the life sciences industry has allowed both high-throughput and bench-top automation to be adopted for increasing laboratory efficiency, improving method optimization for lower LOQ and LOD, reducing typical manual method errors, and reducing repetitive laboratory personnel injuries. Both large and small facilities are looking to add automation to stay competitive and add efficiency.

Q2 Answer:

Molecular diagnostics most certainly will see growth as research pushes further understanding of hereditary diseases with genetics testing, gene-expression profiling, and identification of mutations. New assays using real-time PCR, reverse transcription PCR, digital PCR, combinations of PCR techniques, or maybe even a future generation of PCR will assist as industry pushes for better specificity and higher sensitivity. One of the challenges will be managing the wealth of information produced by highly parallel techniques such as next-gen sequencing, but if tools for data mining and management are paired, there will be a significant potential for this to enhance and influence research. Industry will continue to understand proteins and how they relate to curing disease or identifying disease. Researchers involved in glycomics are uncovering new information daily on the structure of proteins. Characterizing glycans (such as N-glycans for how carbohydrates are linked to proteins) will become even more important as industry moves towards disease biomarkers. Nanobiotechnology may also see more attention as personalized medicine gains importance and requires information on a molecular level within a living organism.s

Richard Krzyzek Ph.D
Chief Scientific Officer
R&D Systems

Q1 Answer:

I consider the dramatic advances in bioinformatics, molecular biology, and monoclonal antibody technology over the last thirty years as the key drivers for the rapid development of the life science industry. The continuing advances in bioinformatics have allowed researchers to analyze large complex datasets to derive biological relationships that need empirical testing. This has created a large demand for analytical reagents such as recombinant proteins, antibodies, and immunoassays.

Technological advances in molecular biology such as PCR, genome sequencing, and recombinant protein expression have paved the way for the exploration of the proteome and enabled the life science industry to provide researchers with a broad offering of recombinant proteins such as cytokines and growth factors. These reagents have not only been instrumental in the advancement of many biological fields, but have also created opportunities for life science companies in other areas such as components of defined cell culture media.

Advances in proteomics have generated an insatiable demand for monoclonal antibodies as well-established tools to characterize the proteome. Cell phenotyping is another rapidly growing market for monoclonal antibodies made possible by advances in flow cytometry instrumentation and fluorescent dye chemistry. Significant improvements in immunization strategies, use of recombinant immunogens, fusion technology, screening methodologies such as microarrays, and the implementation of automation have allowed the life science industry to rapidly expand the availability of well-characterized monoclonal antibodies. Additionally, the emergence of academic groups interested in helping characterize available antibodies under a common testing regimen has helped provide consistency and better definition of antibody reactivities. The emerging technology of generating hybridoma-free monoclonal antibodies from animals having a more diverse immune repertoire than rodents has the potential to provide monoclonal antibodies with a broader range of specificities.

In addition, the immunoassay industry has been transformed by the availability of recombinant proteins and monoclonal antibodies, allowing the development of highly specific immunoassay platforms to satisfy the demands of researchers to quantitate levels of diverse proteins in body fluids. This has catalyzed the rapid advancements of the biomarker field and diagnostics.

Q2 Answer:

a. The increasing demand by researchers to do more with less testing activities and the desire to resolve more complex questions quickly will continue to drive the demand multiplexing reagents. However, the challenge for the life science industry will be to produce multiplex assays that have higher sensitivity, lower sample consumption, lower CVs, rapid high-throughput format, and a broader dynamic range. Currently used multiplexing technologies will not meet all of these expectations and novel technologies will need to be evaluated. Nanoproteomics is a promising emerging analytical platform for the quantitation of proteins that has the potential to meet these specifications. Among the most promising candidates for this analytical platform are nanomaterials such as quantum dots, gold nanoparticles, carbon nanowires, and silicon nanowires. Embracing a nanomaterial analytical platform would be disruptive to the life science industry because more challenging development and manufacturing methods would be required. In the end, any new technology will be powered by the on-board biological, which will characterize the full functionality and value of the assay. These needs will continue to drive the demand for well-characterized reagents for use in immunoassays.

b. Stem cell therapies as well as tissue and organ engineering will be very disruptive to the industry since their reagent demands will be more complex and well defined in composition, and consequently will require significant changes to current manufacturing procedures such as the exclusion of animal-derived components from the production and downstream processing of recombinant proteins. Those companies that will be able to deliver high-quality reagents that meet these specifications will be rewarded.


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