The exchange of opinions motivated by Dr. Baker's article "Paradoxes in carcinogenesis should spur new avenues of research: An historical perspective" illustrates the reasons why the field of cancer research is stuck in a dead end. This paralysis presents a rich opportunity for philosophers, historians and sociologists of science to decipher the whys of this impasse. On the strictly biological front, we suggest to reinstate in cancer research the time proven practice so productive in the physical sciences of discarding wrong hypotheses and theories. We share the suggestion by Dr. Baker to stop trying to unify the two main theories of carcinogenesis, i.e., the Somatic Mutation Theory (SMT) and the Tissue Organization Field Theory (TOFT) because they are incompatible. Dr. Baker suggests breaching the impasse by investing in paradox-driven research. We discuss the barriers to the implementation of this novel strategy, and the significant impact that this strategy will have on knowledge at large and its application for the prevention and cure of cancer.
My last installment in this debate1 focused on the carcinogenesis process as a whole to demonstrate the numerous environmental and physiological factors involved in the multistep processes of carcinogenesis, including the involvement of both somatic mutation and tissue environment dynamics (i.e., Somatic Mutation Theory (SMT) and Tissue Organization Field Theory (TOFT)). In this article, the focus will be primarily in the initiation of carcinogenesis, the all-consuming first step, when the novice cell makes a Faustian bargain2 with the Devil and enters the first of nine circles of Hell.3 Although, there is nothing comedic about the nine prominent changes that have thus far been identified for the development of a malignant tumor.4 The first step is the formation of the initiated cell. By definition, the initiated cell is irreversible due to a newly formed, fixed mutation that is oncogenic. The premise that the origin of the initiated cell occurs by the development of a fixed oncogenic mutation is well founded by a plethora of scientific evidence based mostly on genotoxic studies of chemical and physical carcinogens. The scientific evidence today suggests that the causes and definition of what constitute an initiated cell require updating. Regardless, the formation of the initiated cell is the first (so far) definable step in the pathway of cancer development. Initiation is a process of carcinogenesis that may well be neither the exclusive domain of either SMT or TOFT, but may offer both theories mechanisms on which to expound.
Abstract Paradox-driven cancer research is motivated by paradoxical results under the dominant somatic mutation theory (SMT) of carcinogenesis that can be explained by the alternative tissue organization field theory (TOFT). In contrast, technology-driven cancer research begins with the premise that SMT is correct and seeks to apply new technology to further elucidate SMT. Thus, the ultimate success of technology-driven cancer research is highly dependent on the validity of SMT, which is increasingly questioned by the accrual of paradoxical results. Responses to the original debate article did not challenge any of the paradoxical results and argued, instead, for a compromise theory involving both SMT and TOFT. These responses serve as a springboard for a discussion of additional paradoxes. In addition, I argue that a compromise between SMT and TOFT is not logically consistent and could impede scientific progress.
Editor's Note: The commentary by Stark and Thompson is meant to provide background information for readers of the review by He et al. on the use of abandoned mine drainage for the development of unconventional gas resources. Melissa Stark is the lead for Accenture's New Energy Practice and is the research lead for Accenture's “Water and Shale Gas Development, Leveraging the US experience in new shale developments” report. Some aspects of the commentary are based on that report.
This study focuses on the negative effects of the highly competitive academic environment. We summarized the literature on what consequences an over-competitive system has on the people involved and on the productivity of the system as a whole. We conclude that negative effects outweigh the potential gains which competitive systems bring about. The literature suggests that not only do constant rejections demotivate the majority of academics, but also the funding allocation process in itself seems inefficient. The pressure on academics is so high that we tend to systematically over-estimate our success chances of our funding proposals, manuscripts and promotion requests.
Relatively recent competitions, prizes, and challenges have seen a resurgence in use. They are a driving innovation in a wide array of scientific and engineering arenas. However, not all techniques and opportunities are being taken advantage of. There are many models of competitions that have been studied and used in numerous engineering design challenges. Because of this, we can identify opportunities to also use these models to advance scientific achievements. Competitions are very common in posing engineering design challenges. However, there are relatively few pure science competitions being created outside of the recognition prizes such as the Nobel Prize. We argue that there are models of incentivized innovation that can be used to dramatically advance new scientific discoveries and that in the next decade, we will see a large and rapid increase in the use of incentivized innovation for scientific advancement.
Platelets contain an array of growth factors, extracellular matrix molecules, and other signaling molecules that are released into the injury site upon platelet activation, thus providing the cues needed to help initiate and orchestrate tissue repair. In an effort to harness this activity for therapeutic use, autologous concentrated platelet-rich plasma (PRP) has become a popular therapy, particularly in sports medicine, where the desired outcome is to overcome the body's limitations to tissue repair and accelerate healing. However, the effectiveness of PRP therapies remains controversial due to variable clinical outcomes. Potential sources of variability include the different types of platelet concentrators as well as the inherent variation in patient-to-patient platelet and growth factor quality and quantity. Additionally, PRP, either activated pre- or postinjection, cannot be spatially contained in an injury site and is rapidly resorbed. A further limitation to PRP is that it is not a simple, off-the-shelf solution. We have developed solid, bioactive plasma-based biomaterials (PBMs) that may address these issues. Unlike platelet concentrators, which concentrate the platelets and subsequently discard a significant volume of plasma, we utilize the entire plasma (including the platelets), which contains vital growth factors and other components that are not platelet-derived. Pooled plasma is utilized to reduce PBM lot-to-lot variability. PBMs are inexpensive to manufacture, safe, available as off-the-shelf products, formable into complex 3D shapes, and biodegradable with tunable biomechanical and degradation properties. PBM retention of growth factor activity has been demonstrated with the use of cell proliferation assays. Biocompatibility has been established both in vitro and in vivo. Further, the initial feasibility of PBMs to stimulate the repair of a bone defect was demonstrated in a mouse calvarial defect model. Overall, PBMs represent a platform technology with significant potential to be a disruptive new therapy option in a variety of clinical applications, not only in major clinical markets, but also in third world and developing countries, where the need is high, but where the cost is a barrier to treatment.
Disruptive Science and TechnologyVol. 1, No. 3 EditorialDisruption and Public PolicyAlan J. RussellAlan J. RussellSearch for more papers by this authorPublished Online:1 May 2013https://doi.org/10.1089/dst.2013.1500AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Disruption and Public Policy." , 1(3), p. 117FiguresReferencesRelatedDetailsCited byCognitive Journalism and Its Adaptation of Disruptive TechnologySSRN Electronic Journal Volume 1Issue 3Apr 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:Alan J. Russell.Disruption and Public Policy.Disruptive Science and Technology.Apr 2013.117-117.http://doi.org/10.1089/dst.2013.1500Published in Volume: 1 Issue 3: May 1, 2013PDF download
Aortic stenosis (AS) is a disease of aging, characterized by progressive calcification and fibrosis of the aortic valve and, ultimately, cardiac failure. The onset of symptoms is an indicator of high near-term mortality. The gold standard to treat AS is surgical aortic valve replacement (SAVR), an invasive and risky intervention for many patients who are elderly and have multiple comorbidities. Due to its invasiveness, 30%–40% of patients with symptomatic AS are too sick for SAVR. For those who can tolerate SAVR, however, long-term outcomes are very good. Over the last decade, a push toward less invasive approaches to treat AS has arisen to address a considerable unmet clinical need. Since 2002, a catheter-based approach to aortic valve replacement (TAVR) has led the drive toward less invasive approaches; however, that approach carries a risk of stroke among other complications, and it has uncertain long-term durability. Because of these issues, many cardiologists and cardiac surgeons are reluctant to offer TAVR to those who are healthy enough to undergo SAVR. Herein, we describe a third option for AS patients, one that has potential to enable a safe and effective treatment for a large number of high-risk patients with AS. Known as Aortic Valve Bypass (AVB) (or apicoaortic conduit), this procedure leaves the diseased native valve in place, while creating an alternative left ventricular outflow tract to relieve blood flow obstruction from the stenosed valve. Almost 100 years of physiologic rationale supports the use of AVB. It is durable and halts natural AS. Historic AVB never became popular among surgeons because of its procedural complexity. However, in recent years, a new device (known as the Correx Applicator) that automates the most challenging process of the AVB procedure (i.e., apical coring) is now creating a resurgence of interest in the AVB technique. It allows AVB to be performed on a beating heart and in a less invasive manner than SAVR. Stroke risk and other complications common to both SAVR and TAVR are minimized. In the presence of a markedly simplified AVB procedure, patients with AS now have more treatment options than ever. The comparative effectiveness data for SAVR, TAVR, and Correx AVB may drive new treatment standards in the years ahead.
Genetic Engineering & Biotechnology NewsVol. 33, No. 18 Point of ViewDisrupting Alzheimer's Disease ResearchChallenge Program Aims at Avoiding Impending Epidemic for Aging PopulationMeryl Comer, Maria C. Freire, and Alan J. RussellMeryl ComerSearch for more papers by this author, Maria C. FreireSearch for more papers by this author, and Alan J. RussellSearch for more papers by this authorPublished Online:7 Oct 2013https://doi.org/10.1089/gen.33.18.01AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited by#SocialIT#SocialIT Volume 33Issue 18Oct 2013 Information© 2013 by GEN PublishingTo cite this article:Meryl Comer, Maria C. Freire, and Alan J. Russell.Disrupting Alzheimer's Disease Research.Genetic Engineering & Biotechnology News.Oct 2013.6, 8.http://doi.org/10.1089/gen.33.18.01Published in Volume: 33 Issue 18: October 7, 2013PDF download
Lactobacillus forms a thick, protective biofilm in the female urogenital system that provides protection against bacterial infection. Standard obstetric and gynecologic procedures can disrupt this biofilm, increasing the patient risk for developing infectious complications. The role of biofilms in the female reproductive system was evaluated by performing Medline/PubMed literature searches using the key words biofilm, Lactobacillus, urethral, and vagina. Additional information was evaluated from previously presented doctoral theses and scientific meeting abstracts. The important protective role of Lactobacillus biofilm in the female reproductive tract is supported by research with bacterial vaginosis and sexually transmitted diseases, with mixed data for female urinary-tract infections. Lactobacillus biofilm, therefore, may be a target for treatments when developing treatments to reduce reproductive system infections. Promoting Lactobacillus biofilm growth may also be important for reducing complications after gynecologic surgery and obstetrical procedures that typically disrupt the healthy, protective vaginal biofilm.
Wastewater generated by natural gas extraction from Marcellus Shale activities and abandoned mine drainage (AMD) are the two most significant environmental concerns in Pennsylvania for their potential impacts on surface and groundwater. Reuse of Marcellus Shale wastewater for hydraulic fracturing represent an innovative solution that reduces potential environmental impacts of this industry. Because abundant AMD sources exist in the vicinity of shale gas extraction sites, it would be beneficial to utilize AMD as makeup water for hydraulic fracturing operation and reduce the impacts of this legacy issue from another energy-related industry in the region. This approach would alleviate demand for fresh water by the gas industry, reduce environmental impact of AMD, reduce the cost of water transportation for hydraulic fracturing, reduce the greenhouse gas emissions by the gas industry and reduce the cost of wastewater treatment before reuse for hydraulic fracturing. However, this approach has never before been tried by the unconventional gas industry and barriers to implementation range from technical issues to regulatory concerns. Technical issues include compatibility with fracturing chemicals, excessive scaling and biological growth in the well, and management of solid waste that would be generated by mixing these water sources. Regulatory issues include liability for perpetual AMD treatment that is implied by current regulations. These issues are discussed together with potential solutions based on original studies and review of the literature.
The exchange of opinions motivated by Dr. Baker's article "Paradoxes in carcinogenesis should spur new avenues of research: An historical perspective" illustrates the reasons why the field of cancer research is stuck in a dead end. This paralysis presents a rich opportunity for philosophers, historians and sociologists of science to decipher the whys of this impasse. On the strictly biological front, we suggest to reinstate in cancer research the time proven practice so productive in the physical sciences of discarding wrong hypotheses and theories. We share the suggestion by Dr. Baker to stop trying to unify the two main theories of carcinogenesis, i.e., the Somatic Mutation Theory (SMT) and the Tissue Organization Field Theory (TOFT) because they are incompatible. Dr. Baker suggests breaching the impasse by investing in paradox-driven research. We discuss the barriers to the implementation of this novel strategy, and the significant impact that this strategy will have on knowledge at large and its application for the prevention and cure of cancer.
A major obstacle to winning the war on cancer is a lack of understanding of how cancer develops. The dominant theory for the last 50 years has been the somatic mutation theory (SMT), which says that cancer arises directly from a sequence of genetic changes on a cell that leads to its proliferation. The alternative tissue organization field theory (TOFT) says that cancers arise from a disruption of cell communication needed to maintain normal tissue architecture. A historical background places these theories into perspective. Various experimental results are paradoxical under SMT, but readily explained under TOFT, suggesting paradigm instability. These paradoxical results offer new opportunities for cancer research.
The identification of cancer as a genetic disease is based on the well-documented fact that somatic mutations are required to create the lethal malady. But that is not the whole story. Cancer is also an environmental disease since it takes time to develop with the involvement of numerous environmental factors. There have been many theories of carcinogenesis over the last century that provided much insight, but still fall short of completeness. The Somatic Mutation Theory specifies that cancers arise as a consequence of genetic mutations, but it does not stipulate the mechanisms involved or what else may be required. The Tissue Organization Field Theory specifies that cancers arise as the result of cell communication disruption, but it does not stipulate how this occurs, nor does it clarify what else may be required. Neither theory is independently sufficient based on today's knowledge. The existing experimental evidence clearly supports the Somatic Mutation Theory, and none refutes this theory based on the simple requirement of somatic mutation. The recently proffered Tissue Organization Field Theory has yet to be clearly demonstrated, but there is experimental evidence to lend support to this premise. The root of the problem is the terminology and the clear perception of the processes of carcinogenesis.
Disruptive Science and TechnologyVol. 1, No. 1 EditorialFirst Steps on the Path to Defining Disruptive Science and TechnologyAlan J. RussellAlan J. RussellSearch for more papers by this authorPublished Online:14 May 2012https://doi.org/10.1089/dst.2012.1500AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"First Steps on the Path to Defining Disruptive Science and Technology." , 1(1), pp. 1–2FiguresReferencesRelatedDetailsCited byIJPD inaugural editorial: On priorities and privilege19 December 2020 | International Journal of Paediatric Dentistry, Vol. 31, No. 1Stem cell biomanufacturing under uncertainty: A case study in optimizing red blood cell production7 December 2017 | AIChE Journal, Vol. 64, No. 8The Evolution of Training in Brain Stereotactic Radiosurgery: A Growing Part of Intracranial NeurosurgeryWorld Neurosurgery, Vol. 82, No. 3-4Journals, Repositories, Peer Review, Non-Peer Review, and the Future of Scholarly CommunicationSSRN Electronic Journal, Vol. 3Embracing Debate to Promote Disruptive Science and Technology Alan J. Russell5 December 2012 | Disruptive Science and Technology, Vol. 1, No. 2 Volume 1Issue 1Feb 2012 InformationCopyright 2012, Mary Ann Liebert, Inc.To cite this article:Alan J. Russell.First Steps on the Path to Defining Disruptive Science and Technology.Disruptive Science and Technology.Feb 2012.1-2.http://doi.org/10.1089/dst.2012.1500Published in Volume: 1 Issue 1: May 14, 2012PDF download
Microalgae oil production is the subject of intensive worldwide research and development, with several billion dollars invested in the past few years. Many different approaches and technologies are being investigated: (1) growing microalgae on sunlight and CO2 in enclosed photobioreactors (tubes, bags, panels, etc.) or open ponds; (2) growing algae heterotrophically in the dark on sugar and starches; (3) hybrid systems using both sunlight and sugar or starches, and even (4) processes using artificial lights. Generally, the microalgae strains used in the above systems are isolated from nature, superior strains are selected, and then these are genetically improved for high productivity of vegetable oils (triglycerides) or hydrocarbons. Genetic improvement can include genetic engineering to create microalgae strains that excrete fuel products, which can then be recovered without need to harvest or even produce large amounts of algal biomass. Many types of microalgae are being investigated, and several companies and projects are currently moving to pilot and even large demonstration projects. Over a score of life cycle assessment (LCA) studies on microalgae oil and biofuels production have been recently published, with a majority, but not all, concluding that algae biofuels could substantially reduce greenhouse gas (GHG) emissions, compared to fossil fuels. However, with the exception of fermentation processes (using sugar or starch as inputs), essentially no algae oil is currently produced beyond small amounts for fuel testing. Thus, all LCA studies are based on extrapolations from laboratory experiments, small-scale outdoor studies, and, mainly, on assumptions and projections of future technological advances. A more crucial problem is that most studies have not been based on the detailed engineering designs and systems analyses required to derive energy inputs and mass balances. A preliminary LCA of microalgae oil production using open ponds, based on a recent detailed engineering and economic cost study, is presented. It concludes that algae vegetable oil could be produced with essentially no fossil energy inputs or net GHG emissions, based on realistic productivity, scale, site, and operating assumptions. This LCA will be compared to others available in the open literature.
Properly regulated inflammation facilitates recognition and reaction to injury or infection, but inadequate or overly robust inflammation can lead to disease. Sepsis is an inflammatory disease that accounts for nearly 10% of total U.S. deaths, costing more than $17 billion. Acute inflammation in sepsis may evolve too rapidly to be modulated appropriately, and we suggest that therapies should focus not on abolishing inflammation, but rather on attenuating the positive feedback cycle of inflammation/damage/inflammation. In Gram-negative sepsis, bacterial endotoxin causes inflammation and is driven and regulated by the cytokine tumor necrosis factor-α (TNF-α), which is, in turn, negatively regulated via its endogenous inhibitor, soluble TNF-α receptor (sTNFR). We generated stably gene-modified variants of human HepG2 hepatocytes, using lentiviral constructs coding for mouse sTNFR driven by the constitutive cytomegalovirus promoter, and seeded them in a scaled-down, experimental liver bioreactor. When connected to anesthetized, cannulated rats subjected to endotoxin infusion and maintained solely by the animals' circulation, this biohybrid device elevated circulating sTNFR, reduced the levels of TNF-α and other key inflammatory mediators, alleviated hypotension, and reduced circulating markers of organ damage. This novel class of biohybrid devices may bemodified for patient- and disease-specific application, and, thus, may represent a disruptive strategy that offers the potential for rational inflammation reprogramming.
Disruptive Science and TechnologyVol. 1, No. 2 Debate ResponsesBattling Cancer: In the End What Matters the Most?Eric LagasseEric LagasseSearch for more papers by this authorPublished Online:5 Dec 2012https://doi.org/10.1089/dst.2012.0018AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Battling Cancer: In the End What Matters the Most?." , 1(2), pp. 108–109FiguresReferencesRelatedDetailsCited byCarcinogenesis Marked by Initiation1 May 2013 | Disruptive Science and Technology, Vol. 1, No. 3Paradox-Driven Cancer Research1 May 2013 | Disruptive Science and Technology, Vol. 1, No. 3Embracing Debate to Promote Disruptive Science and Technology5 December 2012 | Disruptive Science and Technology, Vol. 1, No. 2 Volume 1Issue 2Jun 2012 InformationCopyright 2012, Mary Ann Liebert, Inc.To cite this article:Eric Lagasse.Battling Cancer: In the End What Matters the Most?.Disruptive Science and Technology.Jun 2012.108-109.http://doi.org/10.1089/dst.2012.0018Published in Volume: 1 Issue 2: December 5, 2012Online Ahead of Print:August 28, 2012PDF download
The existing paradigm of the scientific literature—individual authoring and editing, parallel review, a format that allows only reading—has not changed in over a century. The barriers to authorship, use, and the creation of scientific works are significant. We developed a new literature format based on an interactive network to address the needs of all parties, from author to user. We began by structuring the writing of text and data for a discipline's needs. Five report types were created, with menus for specific terms and data to allow online, simultaneous, multiauthor writing and editing. A new measurable peer-review process was created. Users can ask questions of reports, and data from multiple reports can be combined. A topic search is associated with automated research tools. We built a prototype that was built and refined based on continuous feedback from surveys, expert panels, presentations, and other feedback mechanisms. In continuous development, the free network World Science (www.world-sci.com) was launched for global beta testing in April 2011, and is now used worldwide. Reports have been written, reviewed, and published within the network or in other journals. Data collected from use and user feedback continue to refine the model. Using methods of metadata storage and analysis, we created a new format for the literature from the front end, modifying creation to use that is efficient and powerful. Because scientific writing is taught during use, the network is being adopted for teaching. We believe that this format will radically alter the creation and use of credible knowledge for the benefit of society. The technology is disruptive to the current publication model and creates new learning, research, and professional opportunities.
