The Butchering Art: Lindsey Fitzharris' book about Joseph Lister and Victorian medicine

Despite my curiosity about biology, I have always been a bit squeamish about human blood and guts. For example, I found the The Knick and Dr. Mutter's Marvels fascinating, but I recoiled at some of the scenes from medical history. I think I was focused on the history and not the grim details when I decided to read Lindsey Fitzharris' new book The Butchering Art: Joseph Lister's Quest to Transform the Grisly World of Victorian Medicine. It is likely that Fitzharris' excellent Twitter feed, where she shares medical oddities and amazing stories from medical history, influenced my decision as well.

The Butchering Art includes a clear and sometimes sobering account of the realities of hospitals during Lister's career. Several major infections plagued hospitals of the era and gave them the nickname of "Death Houses". In addition, the need for bodies for surgeons to practice their craft fueled a profitable trade in grave robbing, body snatching, and even encouraged murder.

Lister's microscope, via Wikimedia Commons

Joseph Lister was raised as a Quaker; Fitzharris suggests that this background informed much of his approach to medicine, especially his compassion to all of his patients, no matter their class or condition. His father, Joseph Jackson has a strong interest in nature and science, likely seeing these as part of god's wonder; this appreciation was instilled in the young Lister. Lister's father was also was an avid microscopist and even invented several improvements for the microscope. At the time, microscopes were merely considered a conversation piece for men of a certain class. Incongruously, Joseph Jackson was a therapeutic nihilist (like many Quakers at the time), "believing that Providence played the most important role in healing." (Considering the types of medical treatments that were popular at the time, the outcomes were probably about even for both therapeutic nihilists and medical interventionists).

This confidence in the powers of microscopy would serve Lister well throughout his medical career. Young Lister brought a microscope to medical school with him. While his instructors noted that it was the best one in the school, they did not yet appreciate what the tool could offer to clinicians and surgeons; in fact, they even viewed it as "a threat to the medical establishment itself." Lister published several scientific manuscript in microscopy journals describing his investigations. This included results on the composition of the iris, which he learned from observing specimens from horses, cats, rabbits, and guinea pigs.

Bringing a scientific and critical eye to medicine was a unique strength of Lister. Throughout his career he found other doctors who approached medicine this way. These included the physiologist William Sharpey and the cutting-edge surgeon James Syme. These men allowed Lister to develop his skills both as an experimentalist and as a surgeon. Lister and Syme were also integral in transforming the approach to medical education.

Lister's carbolic steam spray; from Wellcome images

Lister's work in anti-septic technique was also influenced by the work of Louis Pasteur. By 1865, Lister was experimenting with different methods to create anti-septic environments. He decided to try carbolic acid, which had been used by sewage engineers to counteract the smell of rotting garbage. Lister carefully approached the design of a small clinical trial with bone fractures and had great success. As the anti-septic methods became established through his methodical experimentation, the usual hospital plagues were eliminated from Lister's wards.

Despite the success of his techniques, other surgeons were slow to adopt anti-septic practices. Those that did try the techniques claimed that the results were not convincing. Lister published a series of papers with clear and reproducible methods in the Lancet, which served as an important platform for the debate on anti-septic practices. 

This apprehensiveness to Lister's findings, even in the face of increasing evidence was a major theme of the book, one that fits within the structure of scientific revolutions. There's this scene in the movie 12 Monkeys, where Jeffrey (played by Brad Pitt) talks about the scientific revolution that accompanied germ theory. Jeffrey gives the example of Ignaz Semmelweis, who was generally considered to be crazy for believing in something that couldn't be seen with the naked eye. This allegedly drove Semmelweis to insanity (there is some debate about that idea). Things turned out better for Lister, who eventually became a surgeon to the queen and the namesake of Listerine. 

While the book does include some of the shocking details of surgery before ether and anti-septic, at its core The Butchering Art is a story of a revolutionary doctor who changed the way medicine was taught and practiced. The book was an immensely readable and fascinating look at medical and scientific history.

The genetics of the calico cat

In an earlier post, I detailed the life and work of Nettie Maria Stevens, the namesake of our new calico cat. Nettie Stevens is known for her discovery of the X and Y chromosomes as the basis for sex determination. While researching the post, I found myself in another internet rabbit hole and I wanted to share some of the things I learned about cat genetics because, it turns out, calico cats are an excellent lesson in genetics.

The genetics of cat fur color (like the genetics of human hair color) are rather complex. There are many different genes that create the spectrum of coat colors and patterns found in domestic cats. In other mammals, white fur color alone has been linked to at least six genes (MITF, EDN3, EDNRB, PAX3, SOX10, and SNAI2). For this discussion, I will focus only on the gene loci that create the calico pattern: agouti (A), orange (O), and spotted (S). Based on the combined expression of these genes, some cats are tortoiseshell, a mix of black and orange and some cats are calico, a mix of black, orange, and white. Because the Orange gene is on the X chromosome, most torties and calico cats are female. There are rare cases of male cats with Klinefelter syndrome (XXY) that can have these fur color variants.

Figure 1 Schmidt-Kuntzel, et al., 2009

Agouti (gene name ASIP) encodes a protein that inactivates the melanocortin receptor and thus controls the distribution and amount of pigment cells (melanocytes) in the hair. The Orange gene has not yet been identified, but its position on the X chromosome has been mapped. Interestingly, the MC1R gene, which has been linked to red hair in humans and other mammals, is not involved in the coloring of calico cats because it isn't on the X chromosome. A recent study of the Syrian hamster, which shows sex-linked inheritance of yellow fur color, described the sex-linked yellow gene (Sly) as being independent of MC1R function and not likely homologous to the Orange gene in cats. However, recessive versions of the MC1R allele create orange/amber fur color in Norwegian forest cats. The gene for white spotting (S) has been linked to the KIT locus; more recent publications have shown that a retroviral insertion in the KIT oncogene caused white spotting, with a full insertion leading to the recessive all white mutation.

The genetics of the tortoiseshell/calico cat

If fur color followed the rules of Mendelian genetics, you would expect cats to be only black and white or orange and white, not two or three colors at once. The patterns observed in calico and tortoiseshell cats can be explained by a phenomenon called X chromosome inactivation. Somatic chromosomes come in even pairs, but the sex chromosomes are not created equal. The Y chromosome is rather small and does not encode many genes. In contrast, the X chromosome contains lots of protein-encoding genes. If an XX individual expressed all the genes on both X chromosomes, they would have a huge imbalance in protein expression in comparison with someone with XY. Organisms have different ways to level the compensate for these differences. In mammals, this involves silencing one of the X chromosomes in each cell with the XX genotype. In organisms like the fruit fly, the XY males just double the expression of the genes on the X chromosome.

The specifics of how this happens is actually pretty amazing. (For further details of the process, check out my post on Nessa Carey's book Junk DNA.) In short, a long non-coding RNA known as Xist (X-inactive specific transcript) turns off one copy of the X chromosome in each cell; on the opposite strand of DNA, a gene called Tsix is found. Xist and Tsix have mutually exclusive expression, which ensures that only one X chromosome is inactivated in each cell. X chromosome inactivation occurs at the 8 cell stage of the embryo. Different cells inactivate different copies of the X chromosome, which means some cells express alleles for orange and white and other cells express black and white alleles. These 8 cells then divide and produce the millions of cells that make up a cat. This random pattern of gene inactivation leads to the pattern observed in Nettie and other calicos.

Carbon copy (left) is a clone of Rainbow (right)

Importantly, because these traits are not strictly inherited by classic Mendelian patterns, it makes cloning cats a bit trickier than other animals. As highlighted in the book Frankenstein's Cat, scientists were disappointed when the cloned cat Carbon Copy ended up looking quite different from its clone mother. Had they thought more carefully about the genetics of calico cats, they might have picked a different breed for their experiment!

maneki-neko calico cat figurines are
thought to bring good luck

Calico cats like our Nettie offer excellent lessons in genetics as they higlight X-linked genes and dosage compensation. After all this reading, I think I will take advantage of cat genome sequencing to discover the specific mutations in our cat. I learned more than expected about cat genetics and hope to share these lessons with you soon. For now, if you want to learn more about the genetics of cats, you should check out Herding Hemingway's Cats by Kat Arney.

Caesar's Last Breath: Sam Kean brings his keen eye for storytelling to explore the air around us

I just finished reading Sam Kean's new book Caesar's Last Breath: Decoding the secrets of the air around us. I wasn't planning to write a review, but when I realized my blog has covered every other book by Sam Kean (including Dueling Neurosurgeons and The Violinist's Thumb), I felt like it deserved some attention.

The theme of the book is understanding the molecules that make up our air. Each chapter is devoted to a component or two that is found in the air we breathe. This approach means there is some overlap with Kean's brilliant debut, The Disappearing Spoon. Luckily, the overlap seems only to include the best stories in the history of chemistry and Kean is able to explore the stories further. For example, we get more background on the German chemist Fritz Haber inventor of the process to make ammonia from nitrogen and hydrogen, thus spurring the development of agriculture and chemical weapons. I don't want to spoil it, but if you want a taste, you can check out Kean discussing the story on Radiolab.

Not all of the stories are as serious as Haber's. For example, Kean's chapter on methane allows a moment of silliness in the details of the life of the French performer Le Pétomane, a man who trained himself to fart at will. At his peak, he was the highest paid performer in France, bringing bigger crowds to the Moulin Rouge than even Sarah Bernhardt. 

It is difficult to choose a favorite among the chapters, but if I had to pick just one, it would probably be "Controlled Chaos", which focuses on water and its role in the Industrial Revolution, through the work of James Watt and others to develop steam power and the work of Alfred Nobel to make explosives. Nobel's legacy now is pretty securely tied to the prizes bearing his name. However, during his life time, Nobel's work cost many lives and left him in poor health, guilty and haunted by his reputation as a merchant of death. In fact, this guilt was the impetus for his starting the Nobel prize, much to the chagrin of his family who fought to inherit the wealth.

Because I read so many science books, I often have a sense of déjà vu when reading. However, Caesar's Last Breath included lots of new and interesting tidbits, like the surprising connection between Albert Einstein and refrigerators and the strange history of the manipulation of the weather. Perhaps my only complaint with the book would concern the final chapter on the air on other planets, which felt a bit disconnected both in subject and style.

I highly recommend Caesar's Last Breath for people interested in chemistry or the periodic table as well as those interested in the history of science.

How to Tame a Fox (and Build a Dog): a long term experiment and a story of perseverance and hope

The story of Dmitry Belaraev's long-term experiment in fox domestication was beautifully covered by Scientific American and The Discover Blogs as well as on Radiolab. I found the story and the science behind it fascinating, but I wasn't sure a book was needed to delve further in the story. After I read How to Tame a Fox (and Build a Dog), I learned how wrong I was.

Lee Alan Dugatkin co-authored the book with one of the original researchers, Lyudmila Trut. The authors are able to tell the story of Belaraev's seemingly Quixotic plan to tame foxes in a way that is compelling, even when I knew the major plot points.

The project's hypothesis was simple: continuous breeding of the tamest/gentlest foxes would lead to foxes that behaved like dogs. I found it amazing that they were so committed to scientific rigor that they ran a parallel experiment where they chose the most aggressive foxes. At the time, Belaraev faced obstacles from the ruling Communist party. Today, scientists would also question funding such a long-term experiment. Most geneticists use animals with short lifespans (e.g. fruit flies, C. elegans, yeast) so they can get results quickly and at lower costs. The experiment started producing results far earlier than even the principal investigators would have guessed. Even after a few generations, they found that the foxes showed more dog-like traits (floppy ears, tails, and other classic signs of neotony.) After 10 generations, they found that females went into estrus earlier and some male pups showed changes in fur color.

These changes were all predicted by Belaraev, who had a pretty revolutionary idea at the time, which he called "destabilizing selection". He suggested that the changes that occur in the course of domestication aren't simply due to the accumulation of mutations, but rather changes in the expression of existing genes.

Graphical Abstract from Parker et al Cell Reports 2017

Once genome sequencing arrived on the scene, the domesticated foxes were soon the subject of several studies. The first approach was to compare 700 genetic markers that had been used in the initial dog genome sequence with both the wild and domesticated foxes.  The researchers found several cases of convergence between the two domestication events, which included genetics variations that would ultimately lead to changes in the appearance and behavior of the tame animals. In 2010, a paper in Nature reported the genomic changes that accompanied the domestication of dogs from wolves.  Of course, the research is still in progress. One recent paper in Science suggests that dogs were domesticated in Eurasia and Eastern Asia from 14000 to 6000 years ago. The most recent data (published in my journal Cell Reports) suggest that different breeds of dogs had origins in different geographical locations. Importantly, the work published so far suggests that Belaraev was right: changes in gene expression not just mutations were key to domestication.

Perhaps the most fascinating parts of the book were the details concerning the barriers to science in Soviet-era Russia. These included the domination of genetics by a non-scientist named Trofim Lysenko, who was staunchly opposed to the ideas of Darwin and Mendel; these ideas were gaining acceptance at the time in the West. Lysenko even convinced Lenin that putting seeds in the cold would make crops grow better at low temperatures (they don't). Lysenko fabricated data to support his ideas and those of the party, which devastated Soviet agriculture for decades. Lysenko was celebrated by the Communist party simply for being a peasant and for going against "bourgeois Western science".  Interestingly, Khrushchev's daughter Rada, a journalist who trained as a biologist, argued against Lysenkoism and fought to protect science and the work of Belaraev. I think this serves as another example of why it's best to keep politics out of science (but not science out of politics!) The stories of the suppression of science in the height of soviet Russia are evocative of current anti-science rhetoric in these United States.

One of the reasons that Belaraev was able to persevere in the face of such odds was his enthusiasm and charisma. Belaraev was a social chameleon, who could easily adapt to his audience. These traits made people gravitate towards him and helped him argue for the benefits of the fox experiment to the powers that be. Officially, the rationale of the experiment was to breed foxes that would have more variety in their colors, which would help fetch higher prices for their fur. The domestication experiment was funded despite the crackdown on work in genetics. This isolationism crippled Russian scientists, who were cut off from the science in the rest of the world.

In the late 1980s the fox experiment was 30 years old. The farm started to have some trouble with funding and the researchers had to scale back the experiment. The situation was made worse in 1998 when the Russian economy collapsed. The scientists started sacrificing some of the foxes and selling their pelts. Shortly after this, they contacted a few select media outlets to cover the story, which helped them secure some funding for the project. Today, the experiment has been going on for 60 years, which is a long time for a laboratory experiment, but a short time frame for evolution.

How to Tame a Fox (and Build a Dog) was a fascinating and ultimately hopeful story. Even in such a difficult political climate, this scientist and his visionary experiment were able to persevere with some patience and ingenuity, a message that I think will resonate with scientists that are struggling to stay afloat in 2017.

Exploring the world through the mind of an octopus: review of Sy Montgomery's book

Coming off some recent books about neuroscience and animal cognition, I found The Soul of an Octopus by nature writer Sy Montgomery in the local library. I thought it fit my reading theme nicely, so I decided to give it a try.

Overall, the book is interesting and easy to read. Unlike the books I normally read, the organization is not centered around the scientific themes, but rather towards the author's experience of the wonders of the octopus. The book focuses on the author's visits to the New England Aquarium here in Boston as well as to a few other aquariums around the country (notably the Seattle aquarium, which hosts an octopus blind date on Valentine's Day). She also visits the cephalopod laboratory at Middlebury College, where researchers study octopus cognition using an array of mazes and puzzles.

Octopuses (one thing I learned is that this is the correct form of octopus as it is a Greek derivative, like hippopotamus) are incredibly developed in their cognition. Their nervous system is on par with mammals like dogs in terms of the numbers of neurons. This complexity makes them expert problem solvers – they can use tools to help them catch prey and they can figure out how to remove food from puzzle boxes. They are natural escape artists, which makes it difficult for aquarium staff to keep them caged. YouTube has lots of examples of daring octopus escapes.

I did want to point out a few of the interesting facts I learned from the book. Octopus taste receptors, which are on their suction cups, can pick up taste signals from at least 30 yards. This gives them an excellent sense of changes in their environment. They also have a powerful camouflaging ability, which allows them to change colors very quickly. In the wild, they use this in a variety of predator-prey interactions. In the aquarium setting, the color changes are an indicator of the octopus' mood.

Perhaps the most amazing thing I learned was about octopus ink, which is a complex mixture of molecules. Of course, the list includes melanin, which gives ink its characteristic color; it also contains molecules like tyrosinase, which can irritate the eyes and gills of the surrounding sea life. More surprisingly, tyrosinase has been reported to have effects on oxytocin and vasopressin levels, suggesting that octopus ink could calm the squirted prey. Ink also includes dopamine, a neurotransmitter often called the reward hormone. These features of ink suggest that ink isn't just for defensive purposes, but it may also be used to help them capture prey. This has been observed in some species of squid, but not in octopus.

The book spurred me to look into recent publications on cephalopod neural complexity. One notable paper in Cell shows that cephalopods like the octopus have an unusually high rate of RNA editing. The process is unique to the branch of cephalopods called the coleoids, which are behaviorally complex (some might label them as "smart"). In addition, the sites of genome editing occur most frequently in genes associated with the nervous system. These correlations suggest that the ability to edit their genome is what gives them their complexity. Surprisingly, these changes at the RNA level can be inherited. Of course, this ability has its price. While these cephalopods have greater plasticity of the proteins made by RNA, they have a decreased mutation rate in the protein coding regions of DNA, which is the more traditional fodder for evolutionary variation. For more information on this surprising ability, check out the coverage in The Atlantic and New Scientist.

These stories left me wondering what other sorts of mysteries can be found in the octopus, an organism that is often compared to an alien due to its ability to camouflage rapidly, its knack for squeezing into tight spaces, its unusual defense mechanisms, and its uncanny problem solving. I will be heading soon to the New England aquarium to catch a glimpse of one of the octopuses that the author describes and will keep an eye out for more primary research that explains the mysteries of this amazing creature.

She's a brainiac: taming my amygdala's response to neuroscience

Cerebellar neurons by Ramón y Cajal

The study of the brain has always seemed so inaccessible to me. There is something so meta about it that, frankly, it seems to me that only super advanced beings could think about how our thoughts are formed. I felt comfortable in my single cell universe of cell biology, and I felt like neuroscience was far too intricate and complicated for my brain to handle.

Last year, I started working at Cell Reports, which is a broad science, open access journal. We get submissions from every field of biology. I am a cell biologist by training, so my comfort zone is there, but by new journal has really pushed me to read even more broadly than my previous experience at BBA.

For me, neuroscience papers are harder to access, especially because I have a hard time distinguishing my lateral habenula from my amygdala. To solve this shortcoming, I decided it was time to do some immersion therapy. I've read a few popular science books about the brain before–most memorably Sam Kean's Dueling Neurosurgeons. More recently, I read The Genius of Birds, which taught me a lot about how scientists are approaching experiments with the brain and behavior. These experimental designs are ingenious (more evidence that neuroscientists are just smarter beings), but they can seem a bit funny at times (e.g., mouse behind the wheel). Recently, using high resolution brain imaging like fMRI has allowed researchers to map changes in the brain as people think about people or listen to different types of music or are under the effects of LSD.


To continue my immersion therapy, I have been trying to find good popular science books about the brain. Browsing my local book store, I came across The Brain: The Story of You, by David Eagleman, a neuroscientist and adjunct professor at Stanford University. The book, which is also a PBS series, includes some new research as well as some classic experiments in neuroscience. These classical approaches, which were very well cataloged in The Dueling Neurosurgeons, is to rely on patients that are missing part of their brain and see what sort of behaviors they exhibit. This is certainly a noninvasive approach, which could be considered as a physiologically relevant organ-specific knock out. The problem is that the brain is incredible plastic (that word means something very different in neuroscience) and so it can adapt to the limitations of a missing piece. The other problem is that there are a limited number of people with missing parts to their brains!


Luckily, advances in neuro-imaging and the advent of techniques like optogenetics, have allowed neuroscientists to stray from these classic experimental models. Of course, that doesn't keep Eagleman from telling the crazy stories reminiscent of Oliver Sacks and his contributions to Radiolab. For example, he tells the case of the man who lost his sight at 3 years old and had a stem cell therapy to restore his vision in middle age. The therapy restored the ability of his eyes to receive visual stimuli, but his brain needed to be re-trained to interpret the messages from the eyes. Another fascinating bit was about proprioception, which could be considered the sixth sense that controls your body position. You might not know you have it- until you lose it, but this is what allows us to have fluid movements like walking or biking. There are rare cases of people who have lost this sense and the affected individual has to think carefully when moving and must train themselves to be able to move with some degree of fluidity.

While The Brain probably isn't the best book on the subject, it is very accessible and fun to read and certainly has helped in my immersion therapy. While I can now remember what the amygdala does, I'm still shaky about the lateral habenula or the nucleus accumbens, suggesting that my immersion therapy should continue.

I Contain Multitudes: Ed Yong walks us through the wonders of the microbial world

Science stories about the microbiome seem to be as ubiquitous as microbes themselves. There's good reason: it is fascinating to consider that we are home to a completely invisible zoo of microbes, some of which help us to digest our dinner and some of which change our behavior. This intense curiosity has caused some over-hyping of the power that the microbiome can have and the effects that we can exert upon it.

In his first book, I Contain Multitudes, Ed Yong navigates the complexity of the microbiome with his characteristic writing, which deftly combines the nuts and bolts of the science with the wow and wonder at the diversity of the natural world. He discusses some of the amazingly weird microbial relationships that occur in nature as well as those that happen on and in the human body. He seems to hit all the high points of the microbial world, including the ubiquitous symbiont Wolbachia, which scientists are just starting to exploit in insect populations to fight Dengue and Zika, and the amazing research into the human microbiome, which included the awesome roller derby study.

A major theme of the book is the evolving view of our relationship with microbes. The publication of the first microscopic images of microbes by Antonie van Leeuwenhoek (1673) led to an appreciation that there was more to life than what meets the naked eye. Once germ theory started to take hold in the time of Pasteur (ca. 1850), we started thinking that the microbial world was all bad and needed to be eradicated. As the theory of symbiogenesis started to come into favor, our thinking about microbes changed again, leading us to see that there could be "good" and "bad" microbial interactions. As I discussed in my recent post on symbiotic theory, many scientists placed symbiosis/cooperation in opposition to Darwinism. However, as scientists explore these relationships more deeply, it becomes clear that these relationships are much more complex. Yong writes that symbiosis is conflict; conflict that can never be totally resolved. Thus, it may be time to re-evaluate the language we use to describe these relationships and consider adding new terms to capture the complexity of these interactions.

Ed Yong has a knack for finding unusual stories, thus there is no shortage of fascinating tidbits here
– all clearly explained and well researched. Two in particular captured my imagination: Sodalis and the mealybug; both of these were adapted for his column in The Atlantic, so you can read these to get a sense of the style of the book. Sodalis is a microbe that has been found as both a free living and a symbiotic organism, so it appears to capture the beginnings of a symbiotic relationship! Mealybugs are insects that form a sort of Russian nesting doll of symbiotic interactions (it's bacteria all the way down!). The mealybug has acquired multiple microbes to solve different metabolic problems. In evolutionary terms, Yong reminds us, this is a smart move. Bacteria are quick to adapt and they are legion, so if you have a problem that needs solving, there are likely microbes that have already found a solution. Biotechnologists and synthetic biologists are just starting to exploit the diversity of microbial functions that have evolved over billions of years of natural selection; they are starting to put existing organisms to work at new tasks, like cleaning up oil spills or radioactive waste, or to design and build completely new organisms to do these things or so many more.

We are really just at the beginning of understanding the microbes around us. Most of the recently published human microbiome studies are little more than inventory lists, with some studies attempting to make correlations for differences in why certain populations are associated with certain microbes – sometimes with conflicting conclusions. Yong explains that we simply do not have large enough samples yet to trust the conclusions; for example, if you sampled ten people off the street where 5 were wearing blue and 5 were wearing green, you could find a few striking differences if you ask them enough questions. This means we need to be careful with the conclusions from microbiome studies until we have more data!

Ernst Haeckel's diatoms

I hope you will forgive me, but I need to take a moment to talk about poop. (According to Yong, anyone who studies the microbiome should prepare themselves to have blenders of animal droppings on their lab bench.) The first time I heard about the microbiome, it was in the context of fecal transplants. Here, Ed Yong describes the history of the FMT (fecal matter transplant) and its success in treating antibiotic- resistant C. diff infections. At this point, FMT is not an exact science and thus it has had mixed results. The ultimate goal here is a stool substitute, a "sham-poo" if you will. In this way, each patient can be treated precisely according to their needs and can be treated with the microbe(s) that can help address each problem. This is a long way off, but it is amazing to consider.

Frankly, I enjoyed reading this book immensely. Yong is an incredibly talented writer and reading his work in long form reminded me how far I still have to go as a writer. I remind myself that he has honed his craft for many years and try to use that as an incentive to keep writing!