We can read the steps of the scientific method and know about conventions such as the peer review process but at its core what is science? I have been thinking about this question more and more recently. In trying to pin it down the definition seems to diffuse into a overly abstract statement that resembles something I dislike as a shortcut to thinking and refer to as "bumper sticker philosophy." It seems odd to phrase it this way but science is, in a way, about what works and what doesn't work, and understanding the reasons why what works and what doesn't work in a very rigorous way. Science, ideally, is a careful balance of keeping an open mind, embracing curiosity, taking details seriously, and reasoned agreement and disagreement with others. Then there is the real world human aspect of how science is or is not practiced. Statements such as "believing" in evolution or "believing" in climate change do not sit well in a scientific perspective. In current American English this implies faith in something... However, pointing this out can be misinterpreted and hijacked by people with non-scientific motivations.

At the risk of sounding like a kōan, I thought two famous historical case examples, one from physics and one from biology, that have interested me for different reasons, might provide more of an illustration of what science is then trying to nail down a precise verbal/text definition. However, this comes at the risk of people not being patient enough to read them. Perhaps therein lies part of the modern problem. If it doesn't fit into a snappy short phrase it never reaches most people. I've linked PDFs of the two examples below.

• Special relativity (link to PDF)
• Mendelian genetics (link to PDF)

Right or wrong, I have avoided posting much here about politics; however, I just came across this article that refers to the upcoming March for Science and wanted to share it.

"Let science be science again" by Y. Cheng (http://thebulletin.org/let-science-be-science-again10668)

On a personal note, I (Floyd Reed) am from the rural southern Appalachian mountains. Just to put it bluntly, many of my family and friends that I grew up with are anti-intellectual. Many of these people would now consider me an "out of touch elite" because I am a scientist and a professor at a university while they are the disenfranchised "left-behind working class" to place it into some of the terms used in part of the current political dialogue. In some ways I feel like I have a fairly unique perspective in understanding some of the motivations leading to this. It is not easy to forget, for example, "inbreeding" jokes or condescending comments about my accent as a student within academia and to react by constructing an us-versus-them social polarization, which is then all-to-easily hijacked by politicians and others to further their interests. However, my connection to the same cultural background is also conveniently ignored by the people I grew up with---I am now an "outsider"---because it does not fit into the (overly polarized) social myth being constructed. Coming from this perspective points like this in the article stood out to me.

"Interestingly, both of these criticisms reflect a common misconception: that science is the elite pursuit of the privileged few. ... These folks, mostly men, fiddle on futuristic gadgets in secluded rooms inside ivory towers, high above the dwellings of earthly mortals who are not worth the scientists’ time or attention. However, I know that if I were a white man born and raised in America, I might not have become a scientist. The opportunities and resources America would have offered me might very well have led me to pursue another career path based on my broad interests as a child; ... but, fortunately, they were not prerequisites for a career in science. Science is a great equalizer, not a privilege. I believe in the promise of science because I have lived it. I’ll be marching as a personal testament to the promise, and to help keep it alive."

"Science is a great equalizer because it not only empowers the individual, but also lifts whole communities. It is often less-developed regions that more acutely suffer from the lack of access to science—and more significantly benefit from science’s equalizing power."

I also want to comment on where anti-science views fall within politics and who controls how this is framed. Many of the people reading this may view anti-science sentiments as corresponding with conservative political ideologies. For example, for whatever reasons anti-climate-change has been assigned to, or adopted by, the political right. But it can also be pointed out that if we are defending science from politics the current "liberal/left" also has its share of anti-scientific leanings such as aspects of the GMO crop debate. It is tempting to assign labels to an issue that corresponds to a political axis. Defending science from politics also means not playing into political labeling. Here is another quote from Cheng's article:

"Nature has no political ideology, nor should the interpretation of nature. Traditionally in the United States, basic research has enjoyed bipartisan support because science is nonpartisan. Anti-science views exist on both ends of the political spectrum. ... There have always been opponents of science who try to smear or discredit facts that counter their interest-driven agenda. Supporters of science cannot let the other side frame the debate. Staying silent for fear of being misunderstood is not self-preservation; ... The battle lines are drawn between truth and falsehoods, regardless of rhetoric or ideology. ... When ignorance is touted as a virtue, and anti-intellectualism is encroaching on the very fabric of our society, the fight for the preservation and advancement of science calls for a unified effort from the scientific community, and from supporters of science of every color and creed."

Finally, the term "science" is being thrown around a lot. However, it may mean different things to different people, which can get tricky when assumptions are being made about mutual understanding of the term. It is worth taking some time to think about this. In a future post I want to make some comments about what science is and is not, at least from my perspective.

This is one of those lack-of-time-and-funding free idea posts. I had this idea several years ago but have not been able to act on it with all the other priorities I have to deal with. So, I am throwing it out there in case someone who can wants to explore it. If someone has the time and resources this could be done fairly quickly to see if it might work.

Double stranded RNA triggers the RISC (RNA Induced Silencing Complex) pathway and the cell degrades single stranded RNA that matched the double stranded sequence.

Imagine inverting part of a gene so that the resulting mRNA had a reverse sequence for a stretch of nucleotides, at least 21 nucleotides, seven or eight codons, and preferably longer. This might disrupt the amino acid sequence but if chosen carefully, the right gene and position, the disruptions could be minimal with conservative amino acid changes. It also might be in a UTR without disrupting function too much (or even a "tag" extension to a UTR).  (I am not sure if targeting an mRNA intron sequence would be efficient enough knockdown because splicing may occur at a high enough rate to evade degradation...?)

A homozygote for the sequence inversion could be fine. However, a heterozygote with wildtype could trigger the RISC system if the mRNAs bound together.  This would knockdown expression of the corresponding gene. While it might be viable (which would help to engineer the system in the first place), it could have a very strong fitness effect.

If heterozygotes have a lower fitness than either homozygote you have underdominance, which can be utilized to transform a wild population.

Originally I was thinking along the lines of a more complex two-locus system using phiC31 integration sites for transformations; however, cassette exchange could be used to modify a single locus (e.g., Zhang, X., Koolhaas, W. H., & Schnorrer, F. (2014). A versatile two-step CRISPR-and RMCE-based strategy for efficient genome engineering in Drosophila. G3: Genes| Genomes| Genetics, 4(12), 2409-2418.).