"The recent explosion in the number of retractions in scientific journals is just the tip of the iceberg and a symptom of a greater dysfunction that has been evolving the world of biomedical research say the editors-in-chief of two prominent journals in a presentation before a committee of the National Academy of Sciences (NAS) today.
“Incentives have evolved over the decades to encourage some behaviors that are detrimental to good science,” says Ferric Fang, editor-in-chief of the journal Infection and Immunity, a publication of the American Society for Microbiology (ASM), who is speaking today at the meeting of the Committee of Science, Technology, and Law of the NAS along with Arturo Casadevall, editor-in-chief of mBio®, the ASM’s online, open-access journal.
In the past decade the number of retraction notices for scientific journals has increased more than 10-fold while the number of journals articles published has only increased by 44%. While retractions still represent a very small percentage of the total, the increase is still disturbing because it undermines society’s confidence in scientific results and on public policy decisions that are based on those results, says Casadevall. Some of the retractions are due to simple error but many are a result of misconduct including falsification of data and plagiarism.
More concerning, say the editors, is that this trend may be a symptom of a growing dysfunction in the biomedical sciences, one that needs to be addressed soon. At the heart of the problem is an economic incentive system fueling a hypercompetitive environment that is fostering poor scientific practices, including frank misconduct.
The root of the problem is a lack of sufficient resources to sustain the current enterprise. Too many researchers are competing for too little funding, creating a survival-of-the-fittest, winner-take-all environment where researchers increasingly feel pressure to publish, especially in high-prestige journals....."
Researchers have created a gut-on-a-chip microdevice lined by living human cells that mimics the structure, physiology, and mechanics of the human intestine -- even supporting the growth of living microbes within its luminal space.
"The development of new technologies for production of alternative fuel became necessary to circumvent finite petroleum resources, associate rising costs, and environmental concerns due to rising fossil fuel CO(2) emissions. Several alternatives have been proposed to develop a sustainable industrial society and reduce greenhouse emissions. The idea of biological conversion of CO(2) to fuel and chemicals is receiving increased attention. In particular, the direct conversion of CO(2) with solar energy to biofuel by photosynthetic microorganisms such as microalgae and cyanobacteria has several advantages compared to traditional biofuel production from plant biomass. Photosynthetic microorganisms have higher growth rates compared with plants, and the production systems can be based on non-arable land. The advancement of synthetic biology and genetic manipulation has permitted engineering of cyanobacteria to produce non-natural chemicals typically not produced by these organisms in nature. This review addresses recent publications that utilize different approaches involving engineering cyanobacteria for production of high value chemicals including biofuels."
"Our concepts of biology, evolution and complexity are constrained by having observed only a single instance of life, life on Earth. A truly comparative biology is needed to extend these concepts. Because we can not observe life on other planets, we are left with the alternative of creating artificial life forms on Earth. I will discuss the approach of inoculating evolution by natural selection into the medium of the digital computer. This is not a physical/chemical medium, it is a logical/informational medium. Thus these new instances of evolution are not subject to the same physical laws as organic evolution (e.g., the laws of thermodynamics), and therefore exist in what amounts to another universe, governed by the "physical laws" of the logic of the computer. This exercise gives us a broader perspective on what evolution is and what it does. An evolutionary approach to synthetic biology consists of inoculating the process of evolution by natural selection into an artificial medium. E..."
"Scientists have for the first time created laser light using living biological material: a single human cell and some jellyfish protein.
"Lasers started from physics and are viewed as engineering devices," says Seok-Hyun Yun, an optical physicist at Harvard Medical School and Massachusetts General Hospital in Boston, who created the 'living laser' with his colleague Malte Gather. "This is the first time that we have used biological materials to build a laser and generate light from something that is living." The finding is reported today in Nature Photonics 1."
Infrared spectroscopy allows scientists to analyze protein structure on an ultrafast timescale.
"Proteins can take many different shapes, and those shapes help determine each protein’s function. Analyzing those structures can tell scientists a great deal about how a protein behaves, but many of the methods now used to study structure require proteins to be crystallized or otherwise altered from their natural state...."
"It's not what you know but rather what you don't know that will keep you awake at nights.
That is a good saying that received some validity with a citation in Bloomberg Businessweek of findings by Professor Nick Bostrom, director of the Future of Humanity Institute at Oxford University. Among the dangers - in order of severity - threatening mankind with eminent danger are machine super-intelligence, nanotechnology weaponry, nuclear war, synthetic biology and climate change*. Second on that list is "unknown risks."
In other words, the unknown force over the horizon is what may bring catastrophe. For example, a century ago would scientists have conceived of nuclear war, nanotechnology or even malevolent artificial intelligence?..."
"Microbial production of chemicals is now an attractive alternative to chemical synthesis. Current efforts focus mainly on constructing pathways to produce different types of molecules1, 2, 3. However, there are few strategies for engineering regulatory components to improve product titers and conversion yields of heterologous pathways4. Here we developed a dynamic sensor-regulator system (DSRS) to produce fatty acid–based products in Escherichia coli, and demonstrated its use for biodiesel production. The DSRS uses a transcription factor that senses a key intermediate and dynamically regulates the expression of genes involved in biodiesel production. This DSRS substantially improved the stability of biodiesel-producing strains and increased the titer to 1.5 g/l and the yield threefold to 28% of the theoretical maximum. Given the large number of natural sensors available, this DSRS strategy can be extended to many other biosynthetic pathways to balance metabolism, thereby increasing product titers and conversion yields and stabilizing production hosts...."http://bit.ly/GUDy2L
"As novel scientific achievements such as recombinant DNA technology, stem cells, and most recently, synthetic biology, exit the lab and merge with the outside world, fear has followed them. This fear factor has influenced public perception of most novel scientific endeavors.
Biotechnophobia seems to stem from the fact that the risk is human-made. People are less worried about natural risks, David Ropeik, founder and principal of Ropeik and Associates, a risk management consultancy, wrote in The Guardian.
“Nature can indeed be red in tooth and claw, but new versions of plants, animals, and microorganisms that evolve via Darwinian evolution don’t upset us half as much as hybridization by genetic engineering.” We will need to understand and come to terms with factors that bias our risk perceptions, Ropeik warned, or we may fail to exploit breakthroughs like synthetic life.
There are indeed organizations to assess risk and monitor potential hazards associated with biotechnologies. In October 1974, NIH established the Recombinant DNA Advisory Committee (RAC) to respond to public anxiety about the safety of manipulating genetic material through the use of recombinant DNA techniques.
NIH has assessed its “Guidelines for Research Involving Recombinant DNA” with regard to synthetic biology and found that the distinction between recombinant and synthetic techniques is immaterial in discerning the need for biosafety oversight. Rather it is the biological attributes of the final product that should be taken into account. As part of the assessment it amended the guidelines document to include nucleic acids that are synthesized chemically without the use of recombinant technology.
Yet, as recently as March 13, a group of 111 watchdog organizations including ETC Group and Friends of the Earth issued a report saying that current practices for regulating and assessing biotechnology were inadequate. They called synthetic biology “an extreme form of genetic engineering” and asked for a moratorium on the release and commercial use of synthetic organisms and their products...."
"In this age of deep ecological design aspirations, the range of speculative design projects based on algae technology is growing. Algae are imagined to provide a whole range of solutions, from energy-producing architectural towers, to lights, burgers, skin care products, animal feed, drug factories and bioplastics. It finally appears that the world is turning green.
Literally.
Algae, simple photosynthetic plants that live in water, are among some of the oldest living organisms on earth.
Most species can only be seen with a microscope, but others can form dense mats of vegetation or large underwater forests. During the Archean period, between 3.9 and 3.5 billion years ago, blue-green algae* set the preconditions for modern life by changing the earth’s atmosphere, which was choked with poisonous gases, and turning it into an oxygen-rich environment. Their modern-day descendants can use a range of pigments to harvest specific wavelengths of light to form solid plant matter, or ‘biomass’, by using sunlight and carbon dioxide to produce fuel, water and oxygen..."
The next-generation synthetic biology applications:
Rationally designed families of orthogonal RNA regulators of translation by Mutalik VK, Qi L, Guimaraes JC, Lucks JB, Arkin AP.
"Our ability to routinely engineer genetic networks for applications is limited by the scarcity of highly specific and non-cross-reacting (orthogonal) gene regulators with predictable behavior. Though antisense RNAs are attractive contenders for this purpose, quantitative understanding of their specificity and sequence-function relationship sufficient for their design has been limited. Here, we use rationally designed variants of the RNA-IN-RNA-OUT antisense RNA-mediated translation system from the insertion sequence IS10 to quantify >500 RNA-RNA interactions in Escherichia coli and integrate the data set with sequence-activity modeling to identify the thermodynamic stability of the duplex and the seed region as the key determinants of specificity. Applying this model, we predict the performance of an additional ∼2,600 antisense-regulator pairs, forecast the possibility of large families of orthogonal mutants, and forward engineer and experimentally validate two RNA pairs orthogonal to an existing group of five from the training data set. We discuss the potential use of these regulators in next-generation synthetic biology applications."
"Obtaining a complete transcript of a person’s DNA is getting faster and cheaper, raising ethical and privacy questions that the government must examine, a U.S. presidential commission said.
The panel said today it wants public input on developments in human genome sequencing, including how to balance individual privacy against societal benefits. The Commission for the Study of Bioethical Issues, an advisory panel set up in 2009, plans to send President Barack Obama a report by the end of the year.
“Relatively inexpensive, rapid sequencing of whole human genomes appears not only likely, but imminent,” the commission said in a filing. “This prospect raises many questions for the scientific, medical, ethics and patient communities related to how this information can and ought” to be used and regulated....."
"Biofuels synthesized from renewable resources are of increasing interest because of global energy and environmental problems. Compared to the traditional biofuel, ethanol, higher alcohols such as isobutanol and 1-butanol offer advantages such as higher energy density, lower hygroscopicity, lower vapor pressure, and compatibility with existing transportation infrastructure. Some Clostridia species are known to naturally produce isopropanol and 1-butanol. However, these fuels are not synthesized economically using native organisms. Additionally, other C3-C6 alcohols are not produced in large quantities by natural microorganisms. Synthetic biology offers an alternative approach in which synthetic pathways are engineered into user-friendly hosts for the production of these fuel molecules. These hosts could be readily manipulated to improve the production efficiency. This review summarizes recent progress in the engineering of microorganisms to produce C3-C6 alcohols."
Less than a year after after publication, a technique - genotyping-by-sequencing - to analyze genetic information is taking off because the method is cheap and easy, and it generates terabytes of data.
New method of bacterial cell engineering can produce better, cheaper drug therapies
By Anne Ju "Therapeutic proteins, which provide cutting-edge treatments of cancer, diabetes and countless other diseases, are among today's most widely consumed biopharmaceuticals. By introducing bottom-up carbohydrate engineering into common bacterial cells, Cornell researchers have discovered a way to make these drugs cheaper and safer.
A research team led by Matthew DeLisa, associate professor of chemical and biomolecular engineering, has invented a novel method for engineering human therapeutic glycoproteins simply and quickly using E. coli bacteria as a platform. Their work is detailed online March 25 in Nature Chemical Biology...."
Church lab publications - especially interesting the list of submitted/revision "255. Vigneault F, Laserson U, Simen BB, Lieberman-Aiden E, Egholm M, Church GM (2012) Tracking the dynamics of a human antibody repertoire. (in revision)
254. Jewett MC, Church GM (2012) In vitro integration of ribosomal RNA synthesis, ribosome self-assembly and protein synthesis. Nature (in revision).
253. Carr PA, Wang HH, Sterling B, Isaacs FJ, Xu G, Church GM, Jacobson JM (2012) Enhanced Multiplex Genome Engineering through Oligonucleotide Co-selection (in revision)
252. Juhas M, Eberl L, Church GM (2012) Essential genes as antimicrobial targets and cornerstones of synthetic biology (submitted)
251. Boyle PM, Burrill DR, Inniss MC, Agapakis CM, Deardon A, DeWerd JG, Gedeon MA, Quinn JY, Paull ML, Raman AM, Theilmann MR, Wang L, Winn JC, Medvedik O, Schellenberg K, Haynes KA, Viel A, Brenner TJ, Mathews S, Church GM, Shah JV, Silver PA (2012) Personalized Genetic Engineering of Plants. (submitted)
250. Ball MP*, Thakuria JV*, Zaranek AW*, Clegg T, Rosenbaum AM, Wu X, Angrist M, Bhak J, Bobe J, Callow M, Cano C, Chou MF, Chung WK, Douglas SM, Estep P, Gore A, Hulick P, Labarga A, Lee J, Lunshof J, Kim BC, Kim JI, Li Z, Murray MF, Nilsen GB, Peters B, Raman AM, Reinhoff HY, Robasky K, Wheeler M, Vandewege W, Vorhaus D, Yang JL, Yang L, Aach J, Ashley EA, Drmanac R, Kim SJ, Li JB, Peshkin L, Seidman CE, Seo JS, Zhang K, Rehm HL, Church GM (2012) A Public Resource Facilitating Clinical Use of Genomes (submitted as PNAS inaugural article)
249. Peters BA, Kermani BG, Sparks AB, Alferov O, Hong P, Alexeev A, Jiang Y, Dahl F, Tang YT, Hass J, Robasky K, Zaranek AW, Lee JH, Ball MP, Peterson JE, Perazich H, Yeung G, Liu J, Chen L, Pothuraju K, Konvicka K, Tsoupko-Sitnikov M, Pant KP, Ebert J, Nilsen G, Baccash J, Halpern AL, Church GM, Drmanac R (2012) Clinically accurate genome sequencing and haplotyping from 10-20 human cells using massively parallel short reads on long DNA fragments (submitted to Nature)
248. Wang HH, Kim H, Cong L, Jeong J, Bang D, Church GM (2012) Genome-scale Promoter Engineering by Co-Selection MAGE (Nature Methods in press)
247. Wang HH, Huang PY, Xu G, Haas W, Marblestone A, Li J, Gygi S, Forster A, Jewett MC, Church GM (2012) Multiplexed in vivo His-tagging of enzyme pathways for in vitro single-pot multi-enzyme catalysis. (ACS Synthetic Biology, in press)"
"Significant boosts in the microbial production of clean, green and renewable biodiesel fuel has been achieved with the development of a new technique in synthetic biology by researchers with the U.S. Department of Energy (DOE)'s Joint BioEnergy Institute (JBEI). This new technique – dubbed a dynamic sensor-regulator system (DSRS) – can detect metabolic changes in microbes during the production of fatty acid-based fuels or chemicals and control the expression of genes affecting that production. The result in one demonstration was a threefold increase in the microbial production of biodiesel from glucose."
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