How Many Times Do We Have to Say Something for It to Be True?

“A typewriter is a means of transcribing thought, not expressing it.”
Marshall McLuhan

There is more to good writing than sitting down and typing.  Almost all writing requires research of some kind.  The question is, when have you done enough research?  How I conduct research often depends on what I’m writing.  I tend to research my blog posts as I write them.

However, even research can cause problems, is the information in your reference correct? Previously I wrote about two commonly cited studies that are either miss represented or didn’t exist, Do You Know If Your References Are Biting You?   In my last blog post, Should We Care About Grammar and Structure?, I talked about grammar and its impact on readability.  Specifically, the effect of two spaces vs. one space after the period.

Today in 2020, the style guides say to use one space after the period.  When I was in school, the teachers taught us to use two spaces. When did the rule about spacing at the end of the sentence change? To answer that question, I will probably need a library, since I don’t own every version of every style guide published.

Several articles did explain why the rule changed while searching for when I ran into the same why argument repeatedly.  An article from the Atlantic, Why You Should Never, Ever Use Two Spaces Between Sentences, sums it up nicely.

“To accommodate that machine’s (typewriter) shortcomings, everyone began to type wrong.  … Monospaced type gives you text that looks “loose” and uneven; there’s a lot of white space between characters and words, so it’s more challenging to spot the spaces between sentences immediately. Hence the adoption of the two-space rule–on a typewriter, an extra space after a sentence makes text easier to read.”

Therefore, the only reason we used double-spacing at the end of a sentence is because of typewriters.  Typewriters used monospaced fonts, which produced variable spacing inside of words and sentences.  Because of the variable spacing, people used two spaces at the end of the sentence to enhance readability.

Now, if the typewriter and its monospaced font are the sources of double-spacing, then the appearance of double-spacing should correlate with the rise and fall of the typewriter.  According to A Brief History of Typewriters, Pellegrino Turri built the first functional typewriter in 1808. Commercial typewriter production begins in the 1870s.  The end of the typewriter came about with the advent of the word processor, first, as a standalone device and then as a program on every personal computer. IBM invented the term word processor in the 1960s. By the 1990s–2000s, the typewriter had been almost entirely replaced by the computer. Therefore, the commercial lifespan of the typewriter is about 130 years.

Now let’s look at style guides if the argument about one space versus two spaces is correct. Before and after the lifespan of the typewriter, we should see the rule is for a single space. According to The History and Art of Printing, written in 1771.   The author Philip Luckombe states the rule about spacing after periods is “Another rule that is inculcated into beginners, is, to use an m quadrat after a Full-point:” (page 396) An m quadrat is a larger space.

The print shop at the University of Chicago published the first Chicago Manual of Style in 1906; a pdf copy is available here.  According to the Chicago Manual rule 245 on page 83 “A standard line should have 3-em space between all words not separated by other punctuation points than commas,” With regards to periods the 1906 Chicago Manual states “an em-quad after periods, and exclamation and interrogation points, concluding a sentence.”  3-em is shorthand for 1/3 of an em space.  Therefor the Chicago Manual calls for three spaces after a period.

The above examples show for 100 years before, and at least 36 years after the advent of the typewriter, style guides were recommending multiple spaces at the end of the period.  One could argue that for most of the formalized history of typesetting, the preference has been for multiple spaces after the end of a sentence.  Therefore, the argument that typewriters were the reason for double spacing is not valid.  Double spacing existed because typographers felt it made for an improved reading experience.

Why the rule changed from one space to two is not clear.  One common argument is a single space is cleaner. As Farhad Manjoo states, “A page of text with two spaces between every sentence looks riddled with holes; a page of text with an ordinary space looks just as it should.”  The problem with the idea about holes is that it has been well-known as a potential problem for a long time. 

Again, in The History and Art of Printing, the author talks about the possibility of producing a text that looks full of holes.  “but at the same time, they (young typesetters) should be informed, not to do it (use multiple spaces at the end of a sentence), where an author is too sententious, and makes several short periods in one paragraph.  In such case the blanks of M-quadrats will be contemptuously called Pigeon holes; which, and other such trifles, often betray a compositor’s judgment,” (pages 396-397) Specifically spacing is something authors expected trained typesetters to be aware of and correct.

In Two Spaces – an Old Typists’ Habit? the author blames technology and cost savings, specifically, the linotype and the teletypesetter.  These two pieces of machinery allowed publishers to hire typists to replace typesetters. I find arguments concerning the impact of cost and the loss of skilled expertise much more compelling than the typewriter.

One thing I think the typewriter and early word processors did was confuse people about the separation of content and layout.  The content of a piece of writing is in its words and grammar.  The layout is dependent on the item printed and the audience.  It used to be a common practice to publish science fiction stories in multiple monthly parts in magazines.  Later, these stories were put together and published as books.  The layout between the two publications’ magazines and books was different while the content was identical.

With the creation of things like CSS (Cascading Style Sheets) and variable layouts, people again realize that content is independent of the layout.  The independence of layout from content led to the realization that publishers should structure the layout to the publication type and use. These realizations will likely open the door to future style guide built around research and skilled practice, not cost savings.

For now, we should use one space (I’m sure I will fail at that) because that is what the style guides say.  Not because we no longer use typewriters.  Lastly, repetition never makes something true.

Thanks for Listing to My Musings
The Teaching Cyborg

PS:  If you are interested in pursuing this question further. There are several other articles about the typewriter not being the reason for two spaces at the end of the sentence.  One of them Why two spaces after a period isn’t wrong (or, the lies typographers tell about history) uses several of the same sources as I do. However, the author goes into much greater depth.

Additionally, the author seems to have answered the original question that sent me down this rabbit hole.  The eleventh edition of the Chicago Manual of Style published in 1949 was the first edition to adopt the single space rule.  Another good article about the typewriter not being the source of the two-space rule is One or two spaces after a period? How about three?

Should We Care About Grammar and Structure?

“Every language has a grammar, a set of rules that govern usage and meaning, and literary language is no different. It’s all more or less arbitrary of course, just like language itself.”
Thomas C. Foster

I have written a lot about textbooks, ten blog posts.  Perhaps it is more accurate to say the I have written about the confluence of textbooks, modern technology, and educational practices.  What is a textbook, what should a textbook be, is education or business driving the design of textbooks, do textbooks still have a place in modern education, and should textbooks be digital or physical?

Lately, I have been thinking about grammar and typography with respects to writing and communication.  I try and pay attention to grammar when I write.  I am by no means a grammar expert. I am much more concerned with making sure my arguments and points get across then I am with perfect grammar.  I own a copy of Eats, Shoots & Leaves: The Zero Tolerance Approach to Punctuation, I like the book; however, if it were not for grammar checkers, I would be hopeless when it comes to commas.

I have been thinking a lot about grammar, typography, and layout lately. Mostly because of the humble period.  More precisely, the number of spaces used after the period.  When I was in school, my teachers taught, it would be more accurate to say abusively drilled into us that you always used two spaces after the period. Today it would appear that most style guides suggest using one space after a period. The only exception being the American Psychological Association (APA). However, this seems to have changed with the release of the 7th addition APA standards.

While the argument about double vs. single spaces is old, I have encountered it several times while recently doing research.  I wondered when the period rule changed. Surprisingly I can’t find a date or even decade.  In a lot of the articles about one space or two, the authors focused on explaining how the spacing was the result of “technology.”  I will come back to the technology (typewriter) argument in another blog post.

The argument about two spaces or one comes down to readability. Specifically, how does spacing affect readability?  It turns out there is little actual research looking at the effect of the number of spaces after the period on readability.  A paper published in April of 2018 Are two spaces better than one? The effect of spacing following periods and commas during reading concludes, two spaces.  Yes, I said a paper one.  However, the evidence is currently 100% on the side of two.  More research is needed.

What I found most interesting, however, was an article from the Atlantic The Scientific Case for Two Spaces After a Period A new study proves that half of people are correct. The other is also correct.  After explaining what the article says, the author “explains” why the work is not valid or relevant.  I’m not quite sure whether the author is arguing for irrelevancy or invalidity. The author concludes, “The standard comes down to aesthetics, tradition, conservation of paper and space—basically, the fact that reading is an act of much more than information delivery.”

The author goes on to talk about how people can read sentences without spaces.  He says, “Thai and Chinese are typically written without spaces between words.”  He is in fact correct, people have a tremendous ability to and comprehend regardless of word structure. For example, take the common sentence “Thequickbrownfoxjumpsoverthelazydog.” Or this version “Th qck brwn fx jmps vr th lzy dg.” Or even “7h3 qu1ck br0wn f0x jump5 0v3r 7h3 l4zy d06.” Chance is you can read all these variations.

So, let’s ask since you can read these sentences, does that mean we should write this way?  Think about how much paper we would save if we left out all the vowels.  According to article Vowel Compressibility And The Top 5000 Words In English on average, 31.45% of all characters are vowels. Plugging the textbook Concepts of Biology from the open textbook library into Microsoft Word, we find that Concepts of Biology is 599 pages long with 253,113 words and 1,601,952 characters.  Doing a little math on Concepts of Biology, the textbook has an average of 2674.4 characters per page.  Using 31.45% of all characters are vowels, there are 503,813.9 vowels in Concepts of Biology.  If we left out all the vowels Concepts of Biology would be 188.4 pages shorter. That’s a lot of savings.

Let’s take our question further.  This paragraph comes from page 15 of Concepts of Biology,

“Crl Ws nd th Phylgntc Tr

Th vltnry rltnshps f vrs lf frms n rth cn b smmrzd n  phylgntc tr.  phylgntc tr s  dgrm shwng th vltnry rltnshps mng blgcl spcs bsd n smlrts nd dffrncs n gntc r physcl trts r bth.  phylgntc tr s cmpsd f brnch pnts, r nds, nd brnchs. Th ntrnl nds rprsnt ncstrs nd r pnts n vltn whn, bsd n scntfc vdnc, n ncstr s thght t hv dvrgd t frm tw nw spcs. Th lngth f ch brnch cn b cnsdrd s stmts f rltv tm.”

or if we are going to embrace the idea that spacing and vowels don’t matter and you can still comprehend the meaning then we can write the paragraph like this,

“CrlWsndthPhylgntcTr

Thvltnryrltnshpsfvrslffrmsnrthcnbsmmrzdnphylgntctr.phylgntctrsdgrmshw
ngthvltnryrltnshpsmngblgclspcsbsdnsmlrtsnddffrncsngntcrphyscltrtsrbth.
phylgntctrscmpsdfbrnchpnts,rnds,ndbrnchs.Thntrnlndsrprsntncstrsndrpn
tsnvltnwhn,bsdnscntfcvdnc,nncstrsthghtthvdvrgdtfrmtwnwspcs.Thlngthfch
brnchcnbcnsdrdsstmtsfrltvtm.”

Can you read either of the previous paragraphs? It’s posable you can, it’s also possible you can’t.  Try and read the paragraph; here is the paragraph as it appears in the book.

Carl Woese and the Phylogenetic Tree

The evolutionary relationships of various life forms on Earth can be summarized in a phylogenetic tree. A phylogenetic tree is a diagram showing the evolutionary relationships among biological species based on similarities and differences in genetic or physical traits or both. A phylogenetic tree is composed of branch points, or nodes, and branches. The internal nodes represent ancestors and are points in evolution when, based on scientific evidence, an ancestor is thought to have diverged to form two new species. The length of each branch can be considered as estimates of relative time.”

Was your understanding correct, could you read the paragraph?  Even if you could read the paragraph, can you honestly say we should write this way? When it comes to communication and writing, one of the most important things I ever learned was the idea, “It is not your audience’s job to figure out what you are trying to say, it is your job to make sure they can understand it.”

Therefore, if you are trying to communicate, you should use anything that makes it easier for your audience.  While it is true that your readers don’t need two spaces to read your sentences if it makes it easier on your reader, no matter how small, shouldn’t you do it?  As writers, it is our responsibility to do everything; we can improve our writings readability.  Next time you want to stick rigidly to a rule, ask yourself, are you doing it for you or your audience? If you are writing a textbook, remember its already hard to learn something new, make sure your writing makes it as easy as possible.

Thanks for Listing to My Musings
The Teaching Cyborg 

Building Build, Thyself

“Good buildings come from good people, and all problems are solved by good design.”
Stephen Gardiner

Years ago, when I was in graduate school, an IT technician was repairing the lab internet. He asked me, “So when will we be able to grow cars?”  The first thing that popped into my mind was how complex a modern car is.  According to Toyota, a modern car is made up of 30,000 parts if you count down to the bolts.  Electric vehicles don’t have as many “parts” according to an article in Handelsblatt Today, an electric car has 200 parts while a gas or diesel car has more than a 1000 parts.  I answered, “It will be quite some time before we can grow a car.  There is still a lot of work to do.”

It might seem strange to ask “about growing cars”; however, writers fill science fiction with the unbelievable.  In the television show Earth: final conflict, the alien Taelons grew buildings. The Leviathans are living spaceships in the television series FarScape. While a science fiction show is not the best barometer for what is possible, it’s not a measure of the imposable either.  When the television show Star Trek debut in 1966, most of the technology seemed imposable.  However, a lot of “Star Trek” technology exists now.  Google translate, while not perfect, makes a passable universal translator.  We also have handheld communicators (cell phones) and tablet computers.  There is even a subset of 3D printers that focus on food (the replicator.)

Technology tends to make truth out of our imagination. That technology is often driven by challenging scientific endeavors.  One of the most complex scientific efforts currently being pursued is sending people to Mars.  One of the biggest problems is providing astronauts with safe housing.  Beyond the extremely thin atmosphere on Mars, the surface of the planet has two other significant issues, the temperature, and the surface radiation.  The average daily temperature of Mars is -81° F (-63° C).  While the average yearly surface radiation on Mars is eight rads, on earth, its 0.63 rads.

The surface of Mars is lethal to astronauts.  Currently, the “best” idea for providing protective habitats for astronauts is to bury the habitat under several feet of Martian soil.  The Martian soil would provide insulation and protect against radiation.   However, burying the habitats would require large equipment so that the astronauts can move large quantities of soil. Alternatively, we could send prebuilt habitats with walls that are highly insulated and resistant to radiation.  The exact thickness and weight of the habitats would depend on the material used.

The biggest problem with these ideas is the weight. Either the habitat or the equipment to build the habitat weighs a lot.  It is both expensive and difficult to transport heavy objects.  According to NASA, it currently costs $10,000 per pound to put an object into earth orbit.

So, what does science fiction technology, questions about growing cars, and visiting Mars have to do with each other?  Well, science is again working towards making science fiction reality.  NASA scientists are researching the possibility of using fungus (mushrooms) to grow buildings.  When we think of fungus, especially mushrooms, what you generally picture is just a small part of the whole organism, the fruiting body.  The fruiting body of the mushroom produces mushroom spores and allows the fungus to spread.

The bulk of the mushroom grows underground or inside a decaying log and is called the mycelium, which is a fibrous material composed of hyphae fibers.  The idea is that engineers will seed lightweight shells with spores and dried food.  Then when the structures reach their destination water, collected from the local environment would activate the spores, which grow filling the shell creating rigid, durable, and insulated buildings.

When the building is full-grown, withholding water and nutrients will stop the growth.  Later if the structure is damaged, astronauts can add water and nutrients, and the building will repair itself. Using biologicals materials like funguses to build buildings would have an additional advantage for places like Mars.  If you want to expand a building, add another shell filled with water and nutrients, the mycelium from the old structure will grow into and fill the new one.

The final advantage of biological buildings is that once they are no longer needed or reach the end of their life, they can be composted and used to either make new buildings or grow crops.  Reusing the fungus as nutrients will reduce the production of waste materials and make the site more efficient.

Additionally, using techniques like CRISPR, the Mycelium could be engineered to secret natural resins or rubbers, turning them into complex composite materials. It is even possible that eventually, we could engineer the fungus to grow into specific shapes.   Imagine a giant puffball mushroom engineered to grow into a hollow sphere 10-12 feet in diameter.

In addition to using fungus, other groups are exploring the use of other organisms to build buildings.  A group out of the University of Colorado at Boulder has developed a method using cyanobacterium.  The researchers’ mix cyanobacterium, gelatin, and sand together into a brick-shaped mold.  The bacteria grow into the gelatin, where it uses light and CO2 to produce calcium carbonate.  The result is a rigid cement-like brick after all calcium carbonate is one of the components of cement. 

Additionally, the bricks can heal themselves if cracked or even reproduce themselves if broken in half.   The researches cut bricks in half placed half back in the mold with more gelatin and sand, and the bacteria reformed the brick.

While I don’t expect to be living in a house, I grew myself anytime soon. It is starting to look like science will again make science fiction a reality.  While most of what scientists are developing is for use in resource-poor areas like the moon or Mars. We will see offshoots of this technology in use here on earth.  For instance, the bricks created by cyanobacterium absorb CO2 from the environment, unlike regular cement, which produces CO2.

Additionally, the company Basilisk out of the Netherlands is already selling self-healing concrete, which uses calcium carbonate producing bacteria.  For schools and universities, there is a tremendous research opportunity.  While researchers have established the basic idea behind biological building materials, there is still a lot to learn.  For example, there are large numbers of microorganisms that deposit minerals, which ones work best.  Does a mix of multiple microbes work better than one?  What is the most efficient sand size is it only one size or various sizes? This type of research that involves testing thousands of small permutations is perfect for undergraduate researchers and undergraduate classes.

I don’t know what effect all these biological materials will have on construction, but I’m sure it will be fascinating.  Maybe next time someone asks me, “when will we grow cars?” I will tell them, “I’m not sure, but I can grow your garage.”

Thanks for Listing to My Musings
The Teaching Cyborg

How Genetic Engineering Should Be Done

“As medical research continues and technology enables new breakthroughs, there will be a day when malaria and most all major deadly diseases are eradicated on Earth.”
Peter Diamandis

It seems that I have written about genetic engineering in humans a lot.  Most of the writing has focused on Dr. He Jiankui and his experiments to produce humans genetically resistant to HIV.  For a while, it was not even clear where Dr. Jiankui was, though he was said to be under house arrest. On January 3, 2020, Nature published a news article, “What CRISPR-baby prison sentences mean for research.” This article adds several pieces of information to the CRISPR-baby story.  First, China has confirmed that there was an additional birth.  Dr. Jiankui had previously stated that a second woman was pregnant.  However, the mother was in the earliest stages, so it was not clear whether the pregnancy would carry to term.  We now know that a third child was born.

Second, Chines news announced that Dr. Jiankui and two of his colleges were convicted.  The Chines court said, “in the pursuit of “fame and profit,” He and two colleagues had flouted regulations and research and medical ethics by altering genes in human embryos that were then implanted into two women.” Dr. Jiankui received the most severe sentence of three years in prison while his calibrators received shorter sentences.

While some scientist thinks this is a positive step. “Tang (a science-policy researcher at Fudan University in Shanghai) says the immediate disclosure of the court’s result demonstrates China’s commitment to research ethics. This is a big step forward in promoting responsible research and the ethical use of technology, she says.”  Lu You another scientist worries this could negatively impact other research into CRISPR mediated social health care. “If I were a newcomer, a researcher wishing to start gene-editing research and clinical trials, the case would be enough to alert me to the cost of such violations.”

I suspect that a lot of people will find it surprising that after the controversy over Dr. Jiankui’s use of CRISPR to engineer babies that there is any work going on using CRISPR and humans.  However, not only is their research into using CRISPR to treat human disease, some of this research has reached the stage of clinical trials.  Additionally, this use of CRISPR is a whole different animal from Dr. Jiankui’s work. Now that we have reached the end of Dr. Jiankui’s story, let’s talk about how to do human genetic engineering correctly.

First, when it comes to human genetic engineering, there are two general classifications, heritable and nonheritable. As the name implies heritable means, it can be passed on to children and released into the general population.  In nonheritable genetic engineering, parents cannot pass the genetic changes to their offspring.  In general, the difference between heritable and nonheritable genetic engineering is the cells that scientists genetically engineer.  The nonheritable engineering usually uses cells taken from an adult often adult stem cell.  In both cases, we will be discussing the use of CRISPR to modify adult blood stem cells.

Blood is composed of four components, red blood cells, white blood cells, platelets, and plasma.  The four types of blood cells have a finite lifetime, and the body continually replaces them.  The body uses stem cells to produce new blood cells.  For example, a red blood cell also known as an erythrocyte, develops from the common myeloid progenitor cell (Figure 1 B).  The common myeloid progenitor cell develops from the Hemocytoblast (Figure 1 A), which is a multipotent stem cell.  Hemocytoblasts are a stem cell because when it divides one of the daughter cells regenerates the Hemocytoblast while the other daughter develops into a mature cell type like an erythrocyte.  It is a multipotent stem cell because its progeny can develop into multiple types of cells (Figure 1 D1-10).

A basic diagram of hematopoiesis. Image modified from Hematopoiesis simple.png by Mikael Häggström. Creative Commons Attribution-Share Alike 3.0 Unported.
A basic diagram of hematopoiesis. Image modified from Hematopoiesis simple.png by Mikael Häggström. Creative Commons Attribution-Share Alike 3.0 Unported.

In addition to regenerating themselves and producing a differentiating daughter cell, hemocytoblasts can divide to produce two hemocytoblasts.  Since hemocytoblasts can produce two hemocytoblast stem cells, scientists can expand populations of hemocytoblasts.  The ability to expand the stem cells makes them particularly useful for genetic engineering.

Hemocytoblasts can be clonally grown in culture in a lab.  Growing cells clonally means that the population starts from a single cell. Therefore, all the cells are genetically identical.  The specifics of clonal cell culture are not essential to this article, but you can read the basics here. Clonal cell culture gives us the first advantage over embryotic genetic engineering.  When scientists genetically engineer an embryo, the only way to know if the change was successful in all the cells is to test all the cells, which will destroy the embryo.  With clonal cells, you can test as many of the cells as you want and grow more.  Additionally, since the cells are clonal, you know all the cells in the population are genetically the same. 

The other advantage of genetically engineered hemocytoblasts is that they can be transplanted into patients using the techniques for bone marrow transplantation, which brings us to the current generation of CRISPR mediated medical treatments.

The first clinical trial using CRISPR was carried out by oncologist Lu You at Sichuan University in Chengdu, China.  The plan was to use CRISPR to increase the immune system’s response to aggressive lung cancer.  The researchers removed cells from the patents and then disabled the PD-1 gene, which should enhance the immune response.  Dr. You is currently working on a manuscript describing the results of his work. This experiment is not a surprise; genetic engineering of immune cells for the treatment of cancer has a long history.  What CRISPR has added to the technique is a faster, more accurate way to change the cells.

In addition to the cancer work in China, the US has also approved CRISPR mediated medical treatment.  The treatment we know the most about involves Victoria Gray, who suffers from sickle cell anima.  Sickle cell anime is a painful, debilitating disease that causes red blood cells to become misshapen and sticky.  Victoria Gray volunteered to have her blood stem cells engineered so that the red blood cells express fetal hemoglobin which the doctors hope will compensate for the defective adult hemoglobin that causes sickle cell anima.  Victoria received the transfusion of genetically edited cells early this summer (2019) and the results are quite promising.  Doctors will follow Victoria’s progress for months perhaps even decades.  The researchers will also have to repeat the treatment with additional patients.  Using gene editing to treat sickle cell anime is by no means a done deal but for the first-time individuals that suffer from the illness might have a real permeant treatment.

Hopefully, people will be able to see how the work that scientists are doing to engineer adult cells for the treatment of diseases is different from what Dr. Jiankui did.  One of the most important things we need to get across is that there is nothing wrong with CRISPR or gene editing in general.  Gene editing is a powerful research tool with lots of benefits not only for general research but also for medical treatment.  Scientific techniques are not good or bad by themselves; they are only good or bad in how people use them.  After all, I bet Victoria Gray likes CRISPR.

Thanks for Listing to My Musings
The Teaching Cyborg

Gene Editing in Humans Part Two

“The power to control our species’ genetic future is awesome and terrifying. Deciding how to handle it may be the biggest challenge we have ever faced.”
Jennifer A. Doudna

A year ago, He Jiankui announced that he had used CRISPR to create two gene engineered baby girls.  Since the initial announcement, there has been little new information released.  The government terminated Dr. Jiankui’s lab and research activities. “China’s Vice-Minister of Science and Technology Xu Nanping quickly shut down Dr He’s lab, ordering a full investigation and flagging some form of punishment for the researchers.”  It is also not clear where Dr. Jiankui is located “Hong Kong media reported that the university president, Chen Shiyi, personally flew to Hong Kong to collect and escort Dr He back to Shenzhen, where he was put “under house arrest”. The university denied Dr He was detained, telling the South China Morning Post “nobody’s information is accurate” on Dr He’s whereabouts, but refused to provide any details.

For about a year, this was the state of the information about the first two genetically engineered human beings.  Then early this month (Dec 2019), MIT Technology Review published a series of articles about Dr. Jiankui’s research.  It seems that He Jiankui wrote a 4699-word article titled “Birth of Twins After Genome Editing for HIV Resistance,” while the paper remains unpublished Dr. Jiankui submitted it to Nature and JAMA the Journal of the American Medical Association (China’s CRISPR babies: Read exclusive excerpts from the unseen original research.) Dr. Jiankui’s unpublished work answer several questions that were left unanswered last year.  However, the answers are perhaps more troubling than the speculation.

To understand what Dr. Jiankui was trying to accomplish, we need a little bit of history. Dr. Jiankui calms that he was trying to engineer humans to be resistant to HIV. The HIV-1 virus infects CD4 immune cells.  Over time an individual infected with HIV reaches a point where they cannot produce enough CD4 cells to mount a viable immune response. Leading to the collapse of the immune system and often death by disease.  Around 1996 a naturally occurring mutation in the CCR5 gene was discovered that rendered individuals resistant or possibly immune to infection by the HIV-1 virus.  The CCD5 mutation is a deletion of 32 base pairs (called Δ32) in the coding sequence of the CCR5 gene.  (Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection.)

The Δ32 mutation makes it so that the HIV-1 virus can’t bind to the CCR5 protein.  Since the HIV-1 virus uses the CCR5 receptor to enter cells, this mutation renders cells resistant or immune to infection by HIV-1.  According to his paper, Dr. Jiankui used the CRISPR technology to engineer the CCR5-Δ32 mutation into the in-vitro fertilized embryos of a couple where the husband was HIV positive, and the wife was HIV negative. The genetic change, in turn, would confer immunity to the children born from these embryos.

In the abstract, Dr. Jiankui says they were successful in editing the CCR5 gene.  “Genomic sequencing during pre-implantation genetic testing and after birth confirmed that the twins’ CCR5 genes were edited successfully and are thus expected to confer either complete or partial HIV resistance.” (China’s CRISPR babies: Read exclusive excerpts from the unseen original research) However, the actual data in the paper shows that one of the embryos has a frameshift mutation in the CCR5 gene, while the second embryo has a 15 bp delegation.  While both mutations cause changes in the CCR5 protein, they do not create the same disruption as the CCR5-Δ32 mutation.  It is not clear that these mutations will confer immunity to HIV since not every single mutation in CCR5 confers HIV immunity.  Beyond the question of the effectiveness of the created mutations, new research suggests that being homozygous for the CCR5-Δ32 mutation leads to a decrees in life expectancy (CCR5-∆32 is deleterious in the homozygous state in humans.)  Additionally, it appears that the cells in the embryos may not have all changed to the same extent leading to mosaics.

In addition to the potentially harmful nature of CCR5 mutations, there is a question about the type of genetic engineering.  If you are going to induce a mutation in a gene because of an observed effect, you need to create the same mutation that caused the original effect, not a similar mutation.  The reason is twofold one if you create a new mutation, you don’t know that the new mutation will have the same effect as the old one.  Two of the new mutation could cause a new and unintended consequence that the original mutation did not have.

Now at a first pass, Dr. Jiankui’s motives sound reasonable and altruistic.  He is trying to help a couple that is HIV positive have children.  Dr. Jiankui even states in his abstract, “Millions of children are born annually with inherited genetic diseases or infectious diseases acquired from parents.”  (China’s CRISPR babies: Read exclusive excerpts from the unseen original research) As stated by Rita Vassena, scientific director of the Eugin Group, there are well-established techniques to prevent transmission of HIV from parent to offspring. 

“It is worth remembering that HIV infection is not passed on through generations like a genetic disease; the embryo needs to “catch” the infection. For this reason, preventive measures such as controlling the viral load of the patient with appropriate drugs, and careful handling of the gametes during IVF, can avoid contagion very efficiently.” (China’s CRISPR babies: Read exclusive excerpts from the unseen original research

From a medical point of view, it is rarely if ever considered acceptable to use an experimental and potentially dangers technique when effective options already exist.

Beyond the question of whether the technology was ready, Dr. Jianjui’s foray into genetic engineering brings into sharp focus a question about the utilization of genetic engineering.  Dr. Jianhui attempted to create a new biological function in the twins.  He tried to engineer viral resistance.  What makes this especially troubling is that while we know that CCR5-Δ32 confers resistance to HIV-1 research into the normal biological functions of CCR5 is still ongoing.  The work showing that being homozygous for the CCR5-Δ32 can be harmful to the life span was published this year (2019). Instead of trying to create something “new,” why didn’t Dr. Jianjui try and fix a “broken” gene.

If Dr. Jianjui had at least tried to use genetic engineering to reverse a disease-causing mutation to the normal function, he would not have had to deal with the potential conquests of changing a gene function he would have restored it to normal function.  While this article should make it clear that gene-editing technology is not yet specific enough for reproductive genetic engineering, at the rate the technology is improving, it will not be long before we the technology can make specific changes in an embryo without producing additional defects.

A companion article also from the MIT Technology Review Opinion: We need to know what happened to CRISPR twins Lulu and Nana States that Dr. Jianjui’s papers need to be made public.  Specifically, Dr. Kiran Musunuru says, “Why must the information be public? It’s because He’s work reveals serious, unresolved safety concerns. It’s not clear that any effort to directly edit human embryos, even if done ethically and with full social approval, can reliably avoid these problems.”  While I think Dr. Musunuru’s interpretation is a little extreme.  I don’t believe Dr. Jianjui had a good enough grasp of what he was trying to do to use his research as a cornerstone of the technology limits.  After all, most of the information uncovered in his unpublished work is in aliment with the concerns and beliefs put forward by the scientist when human engineering was first made public.  I do agree that we need to discuss the uses and potentials of genetic engineering.

However, for people to have discussions about the ethics of genetic engineering, people need to understand the basics of genetics and genetic engineering.  Humans have been using genetic engineering since we planted our first crops and domesticated the first animals.  Our faithful companion, the dog, is the product of thousands of years of genetic engineering.  We are entering a point when we can change our ecosystem and ourselves at a rate faster than ever before. However, how much does the general public know about genetics?  Can we make a legitimate decision about genetic engineering if we don’t even understand the basics of what is going on?

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The Teaching Cyborg

Misconceptions in Cell Biology

“Every living thing is made of cells, and everything a living thing does is done by the cells that make it up.”
L.L. Larison Cudmore

Cells are the building blocks of all biology.  Every living organism is composed of cells.  All cells came from preexisting cells.  If you are a trained biologist, you recognize the last two sentences as The Cell Theory, one of the core theories of modern biology.  A lot of The Cell Theory seems basic considering what we know.  However, remember cells are smaller than can be seen by the naked eye.  Until the invention of microscopes, we didn’t even know cells existed.  The word cell was first used by Robert Hooke in the 1660s while examining thin slices of cork.  Hooke used the word cell to describe the structures he observed because they reminded him of the rooms of monks.

Additionally, it wasn’t until Loise Pasteur’s famous swan-necked flask experiment in 1859 that the idea of spontaneous generation, life spontaneous occurring out of organic material, was disproven.  Therefore, every cell must come from a preexisting cell. With the importance of The Cell Theory, it is not surprising that students spend a lot of time learning about the structure, function, and behavior of cells.  However, because cells are not visible to the naked eye, it is not surprising that many students have misconceptions concerning cells.

What is a misconception? Scientific misconceptions “are commonly held beliefs about science that have no basis in actual scientific fact. Scientific misconceptions can also refer to preconceived notions based on religious and/or cultural influences. Many scientific misconceptions occur because of faulty teaching styles and the sometimes-distancing nature of true scientific texts.”  When we teach students biology, how good are we at dealing with misconceptions?  The critical questions are what the student’s misconceptions are and how do we deal with them?

Musa Dikmenli looked at the misconceptions that student teachers had in his article Misconceptions of cell division held by student teachers in biology: A drawing analysis.  In the study, Dikmenli examined the understanding of 124 student teachers in cell division.  According to the study, these student teachers “had studied cell division in cytology, genetics, and molecular biology, as a school subject during various semesters.”  Therefore, the student teachers had already studied cell division at the college level.

At a basic level, cell division is the process of a single cell dividing to form two cells.  Scientists organize cell division (the cell cycle) into 5 phases Interphase, Prophase, Metaphase, Anaphase, and Telophase.  The cell cycle is often depicted using a circle. 

Figure of the cell cycle at different levels of detail. Created by PJ Bennett
Figure of the cell cycle at different levels of detail. Created by PJ Bennett

Instead of answering quiz questions or writing essays, the students were “asked to draw mitosis and meiosis in a cell on a blank piece of A4-sized paper. The participants were informed about the drawing method before this application.” (Dikmenli) The use of drawing as an analysis method has several advantages.  The most important of which is that it can be used across languages and by students in multiple nationalities.

After analyzing the drawings, almost half of the student teachers had misconceptions about cell division.  Some of the most come misconceptions are, when DNA synthesis occurs during mitosis and mistakes about the ploidy, the number of chromosome copies, during meiosis.  The research results mean that individuals that are going to teach biology at the primary and high school level are likely to pass their misconceptions along to their students.

So, where does the problem with student misconceptions start?  Students learn misconceptions from their teacher about cell division.  However, the teachers all have biology degrees from colleges, and their college faculty failed to address their misconceptions. However, perhaps we are not asking the correct questions.  Instead of trying to decide who, K-12 or College, is responsible for correcting student misconceptions, we should ask why students get through any level of school with misconceptions?

I can hear all the teachers now, while obviously, students get through school with misconceptions because it’s difficult to correct misconceptions. However, we know a lot about teaching to correct misconceptions.  Professor Taylor presents one method, refutational teaching in the blog post GUEST POST: How to Help Students Overcome Misconceptions.  With a quick Google search, you can find other supported methods.  In all cases getting the student to overcome the misconception, the student must actively acknowledge the misconception while confronting countering facts.

It is unlikely that the problem is that it is hard to teach to misconceptions, let’s be honest most teachers at any level are willing to use whatever techniques work.  No, I suspect the real problem is that most teachers don’t realize their students have misconceptions. So, then the real questions are why instructors don’t realize students have misconceptions.  In this case, I suspect it is the method of assessment.

Most classroom assignments and assessments ask the students to provide the “right” answer.  The right answer is especially prevalent in the large lecture class where multiple-choice questions are common.  However, the fact that a recent review article A Review of Students’ Common Misconceptions in Science And Their Diagnostic Assessment Tools covers 111 research articles suggest that identifying misconceptions is not complicated if teachers use the correct methods.  Therefore, the incorporation of the proper assessment methods alongside teachers’ standard methods will help teachers identify student misconceptions.

However, it is not good enough to identify misconceptions. The misconceptions must be identified early enough in the course so the teacher can address them.  Finding misconceptions is a perfect justification for course pretests either comprehensively at the beginning of the course or smaller pretests at the start of unites.  In an ideal world, pretests would be a resource that departments or schools would build, maintain and make available to their teachers ideally as a question bank.  Until schools provide resources to identify misconceptions, think about adding a pretest to determine your student’s misconceptions.  It will help you do a better job in the classroom

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The Teaching Cyborg

Double-Blind Education

“It is a capital mistake to theorize before one has data.”
Arthur Conan Doyle (via Sherlock Holmes)

Several years ago, I was attending a weekly Discipline-Based Educational Research (DBER) meeting. Two senior faculty members led and organized the weekly meetings.  Both faculty members had trained in STEM disciplines.  One had received their educational research training through a now-defunct National Science Foundation (NSF) program, while the other was mostly self-taught through multiple calibrations with educational researchers.

The group was discussing the design of a research study that the Biology department was going to conduct.  One of the senior faculty members said if they were serious, they would design a double-blind study.  The other senior faculty member said that not only should they not do a double-blind study, but a double-blind study was likely a bad idea. I don’t recall the argument over double-blind studies in education ever getting resolved. We also never found out why one of the faculty members thought double-blind studies were a bad idea in educational research.

Double-blind studies are a way to remove bias. Most people know about them from drug trials.  Educational reform is not likely to accidentally kill someone if an incorrect idea gets implemented due to a bias in the research.  However, a person’s experiences during their education will certainly have a lifelong impact.  While double-blind studies might be overkill in education research, there is the question of what is enough.  As I have said before, it is the job of educators to provide the best educational experience possible; this should extend to our research.

How do faculty know how they should teach? What research should faculty members use?  Should we be concerned with the quality of educational research? Let me tell you a story (the names have been changed to protect the useless).  A colleague of mine was looking for an initial research project for a graduate student. My college told me about a piece of educational “research” that was making the rounds on his campus.  Alice, a well-respected STEM (Science Technology Engineering and Math) faculty member, had observed her class.  She noted what methods of note-taking her students were using.  At the end of the semester, she compared the method of notetaking to the student’s grade. On average, the students that used the looking glass method of notetaking had grades that avraged one letter grade lower than the other method of notetaking.

Alice told this finding to a friend the Mad Hatter, a DBER (Discipline-Based Education Research) expert.  The Mad Hatter was so impressed with the result that he immediately started telling everyone about it and including it in all his talks.  Now because Alice did her study on the spur of the moment, she did not get research approval and signed participation agreements.  The lack of paperwork meant that Alice couldn’t publish her results.  With such a huge effect, my colleague thought repeating this study with the correct permissions so that it could be published would be perfect for a graduate student.

They set-up the study; this time, to assess what methods the students were using to take notes, they videotaped each class period.  Additionally, the researchers conducted a couple of short questioners and interviewed a selection of the students.  After a full semester of observation, the graduate students analyzed the data. The result, there was no significant difference between looking glass notetaking and all the other types.  Just a little while ago, I saw a talk by the Mad Hatter. It still included Alice’s initial results.  Now the interesting thing is neither Alice nor the Mad Hatter would have excepted Alice’s notetaking research methodology if it was a research project in their STEM discipline.  However, as an educational research project, they were both willing to take the notetaking results as gospel.

While there is a lot of proper educational research, researchers have suggested that a lot of faculty and policymakers have a low bar for what is acceptable educational research.  The authors of We Must Raise the Bar for Evidence in Education suggest a solution to this low bar in educational research.  Their recommendation is to change what we except as the basic requirement of educational research.  Most of the author’s suggestions center around eliminating bias (the idea at the core of the double-blind study) their first suggestion is,

“to disentangle whether a practice causes improvement or is merely associated with it, we need to use research methods that can reliably identify causal relationships. And the best way to determine whether a practice causes an outcome is to conduct a randomized controlled trial (or “RCT,” meaning participants were randomly assigned to being exposed to the practice under study or not being exposed to it).”

One of the biggest problems with human research, which includes educational research, is the variability in the student population.  As so many people are fond of saying, we are all individuals.  By randomly assigning individuals to a group, you avoid the issue of concentrating traits in one group. 

Their second suggestion is, “policymakers and practitioners evaluating research studies should have more confidence in studies where the same findings have been observed multiple times in different settings with large samples.”  The more times you observe something, the more likely it is to be true (there is an argument against this, but I will leave that for another time.)

Lastly, the authors suggest, “we can have much more faith in a study’s findings when they are preregistered. That is, researchers publicly post what their hypotheses are and exactly how they will evaluate each one before they have examined their data.”  Preregistration is a lot like the educational practice used with student response systems were the student/researcher is less likely to delude themselves about the results if they must commit to an idea ahead of time.

If we are going to provide the best educational experiences for our students, we need to know what the best educational experiences are.  However, it is not enough to conduct studies. We need to be as rigorous as possible in our studies.  The next time you perform an educational research project, take a minute, and ask yourself how I can make this study more rigorous.  Not only will your students benefit, so will your colleagues. Thanks for Listing to My Mussing
The teaching Cyborg