This week, a new study published in PLOS Pathogens reported how otherwise benign, commensal E. coli can evolve before our eyes into a malicious pathogen. In this study, researchers cultured E. coli with the mouse immune cells that essentially eat them when found in the body; the macrophages. The co-culture was diluted daily. This would give the bacterial cells a constant source of fresh nutrients. Under constant threat of attack by the immune cells, the E. coli were under ‘continual selective pressures’. A few days of these living conditions caused positive selection of genetic mutations that now allowed the bacteria to evade macrophages. Seven new types of E. coli were identified through this screen and the genomes were sequenced to find the sources of the mutations.
Here are some problems…
E. coli were continually in contact with macrophages in this study. This is very unrealistic and the authors acknowledge this, saying:
We note that in the context of a real infection repeated contact with macrophages will not likely occur with a similar period as the one in this experimental setup.
Another quick problem noticed is that these bacterial cells were growing in an otherwise optimal environment; nutrients were replenished everyday. Again, this is not going to happen in nature. To put this into focus, it would be like winning the lottery jackpot every drawing for a month. In other words, it is not likely.
Under these experimental conditions, researchers were able to force these bacteria to change or die. As in every other challenge faced for over 2 billion years, the E. coli rose to the challenge and did so quickly.
So, congratulations to the authors. You did the expected and got the expected. But hold on; this study did do something really nice. It allows researchers to see the kind of mutations occurring that allow seemingly nice bacteria to become less so. Yet again, we learn from bacterial superstar, E. coli.
The Bush Report as it is known was proposed before the end of World War II so specifics were not the objective of this particular report. This report was more ideological than would be delivered to the White House any other time in history. Here are some more quotes from the report (bold added by me to emphasize important parts).
The Importance of Basic Research
Basic research is performed without thought of practical ends. It results in general knowledge and an understanding of nature and its laws. This general knowledge provides the means of answering a large number of important practical problems, though it may not give a complete specific answer to any one of them. The function of applied research is to provide such complete answers. The scientist doing basic research may not be at all interested in the practical applications of his work, yet the further progress of industrial development would eventually stagnate if basic scientific research were long neglected.
From my time on the inside (assisting DOE’s Office of Science), I know one of the highest priorities of our government is to move the knowledge discovered through basic research into applications that are attractive to industry. The Executive Branch understands that future economic growth is intimately tied to research being conducted today. Any short-sighted moves by the Legislative Branch to make our R&D funding stagnate will have grave consequences for the country in the future when innovations attractive to industry come from overseas.
This is reiterated later in the report section:
A nation which depends upon others for its new basic scientific knowledge will be slow in its industrial progress and weak in its competitive position in world trade, regardless of its mechanical skill.
What are we to do when industry looks to capitalize on innovations from countries such as India or China? Please don’t make me say I told you so…
As my students know very well, I love the whole idea of TED. “Ideas worth spreading” is their mantra and it fits. I just finished watching a TEDMED talk by Harvard biologist E. O. Wilson from 2012 that I have watched several times before entitled, “Advice to Young Scientists”. However, this time through extra digging, I found a short Q & A that followed that talk in which Wilson elaborates on why imagination is so important in science. Expounding on the words of Einstein, Wilson says, paraphrasing, that a scientist must think like a poet and work like a bookkeeper. Creativity and imagination are essential and scientific training makes the discoveries possible.
“New frontiers of the mind are before us, and if they are pioneered with the same vision, boldness, and drive with which we have waged this war we can create a fuller and more fruitful employment and a fuller and more fruitful life.”–
Almost 70 years later, I feel Bush’s words and recommendations within the Report ring just as relevant. In a time when developed countries have increased funding for research and development in FY2012, TWO countries stood out like sore thumbs for decreasing federal research dollars; the United States and Canada. I wish this report could be redistributed to all members of Congress. In this post, I want to bring attention to some of the most ironic/prophetic points. Let’s get right to it…
The responsibility for basic research in medicine and the underlying sciences, so essential to progress in the war against disease, falls primarily upon the medical schools and universities. Yet we find that the traditional sources of support for medical research in the medical schools and universities, largely endowment income, foundation grants, and private donations, are diminishing and there is no immediate prospect of a change in this trend. Meanwhile, the cost of medical research has been rising. If we are to maintain the progress in medicine which has marked the last 25 years, the Government should extend financial support to basic medical research in the medical schools and in universities.
Bush spoke of the great advancement made in antibiotics with the discovery of penicillin. Today, this quote still rings true, certainly with the growing threat of antibiotic resistant pathogens.
How do we increase this scientific capital? First, we must have plenty of men and women trained in science, for upon them depends both the creation of new knowledge and its application to practical purposes. Second, we must strengthen the centers of basic research which are principally the colleges, universities, and research institutes. These institutions provide the environment which is most conducive to the creation of new scientific knowledge and least under pressure for immediate, tangible results. With some notable exceptions, most research in industry and Government involves application of existing scientific knowledge to practical problems. It is only the colleges, universities, and a few research institutes that devote most of their research efforts to expanding the frontiers of knowledge.
Thank you, Congress, for your objective and far-sighted vision showing the nation is your top priority and you are looking out for its best interest. The most recent survey data from the National Science Foundation shows the general public overwhelmingly supports federal funding of basic research:
Since 1985, NSF surveys have asked Americans whether, “even if it brings no immediate benefits, scientific research that advances the frontiers of knowledge is necessary and should be supported by the federal government.” In 2010, 82% agreed or strongly agreed with this statement; 14% disagreed.
Not only does the public support federal funding for science and engineering research, they also hold high esteem for scientists, second only to firefighters and ahead of doctors, teachers, and members of the clergy. In another section, 91% of surveyed Americans are at least moderately interested in scientific discoveries. So, there is hope Americans can become more science literate.
Sequestration takes toll on research, education (universityofcalifornia.edu)
Today, my wife and almost five-year-old left for a well-deserved vacation and by extension I’m on vacation until they return. So, what did I do first after they left? I watched a great video that I had in my ‘Watch Later’ list. It was a back-and-forth between funnyman Stephen Colbert and Hayden Planetarium Director Neil deGrasse Tyson. Dr. Tyson raised a great and insightful point about the state of science and the lack of science literacy in America.
As an adjunct professor in health science research, my first priority is to increase the general science literacy of my students so they can make more knowledgable decisions based upon logic and not based upon the opinions of others. One of the first lectures I give elaborates on what exactly science is and is not. Science is not magic. In fact, science is the opposite of magic. Unfortunately, most of the breakthroughs and discoveries are not easily or not well communicated to the public. This gap in knowledge between the scientists and the public leads to a misunderstanding of what the scientists are actually doing. When the new knowledge goes over the heads of the people it makes science a mystery. Thus, to most of the general public, science is not just a mystery, it might as well be magical.
This gap between the truth about science and the perception of science creates a sense of mistrust. We need to do better.
The ability to study the living without destroying it has been the goal of many scientists for decades. A new article in ACS Nano has paved the road towards noninvasive cellular-level examination. The only true way to study cellular dynamics is to study a single cell over time (temporally). The reason for this is the heterogeneous nature of any cell culture because no two cells are identical spatially and temporally. Each individual cell has its own set of experiences that has generated its current molecular inventory, ie. RNA molecules, metabolites, proteins, sugars, lipids, etc. Studying a community of cells gives rise to noise that makes finding significant differences incredibly difficult.
In the article entitled Compartmental Genomics in Living Cells Revealed by Single-Cell Nanobiopsy, the authors used a kind of microscopy called scanning ion conductance microscopy, or SICM, that allows for continuous sampling of a single cell over time. The authors used a nanopipette as part of the SICM and combined this with sensitive sequencing techniques resulting in a high resolution look at what genes are being expressed over time into RNA molecules. Furthermore, this technique was used to study the genomic information of individual mitochondria within a single cell without also studying the nuclear material. In other words, this new technique has resulted in the ability to not only study cellular dynamics, but go beyond that and study subcellular dynamics.
This breakthrough will have impacts across many fields from cancer biology to improving climate models.
Paolo Actis, Michelle M. Maalouf, Hyunsung John Kim, Akshar Lohith, Boaz Vilozny, R. Adam Seger, & Nader Pourmand (2013). Compartmental Genomics in Living Cells Revealed by Single-Cell Nanobiopsy ACS Nano DOI: 10.1021/nn405097u