Recognition for Beth’s Wikipedia work

25 June 2018 at 21:48 | Posted in Circadian rhythm, DSPS | Leave a comment

In addition to founding this blog, Beth MacDonald was also very active in editing the Wikipedia articles on circadian rhythms. She worked under the pseudonym Hordaland. Last year I was contacted by two researchers in the field of the history of science, Omer Benjakob and Rona Aviram. They were studying the contributions to scientific pages on Wikipedia with a particular focus on the area of circadian rhythms. They had found a large number of edits by the user Hordaland and asked if I could confirm that Hordaland was actually Beth (who had died a few months before). I confirmed their attribution and in subsequent emails answered some of their questions about Beth and her work.

A few weeks ago I received another email from the researchers saying that they had published their research in the Journal of Biological Rhythms [1]. Their article details Beth’s amazing contributions to the Wikipedia articles. I know Beth would have been thrilled to see her name appear in such a prestigious journal on circadian rhythms. It is a fitting tribute to a pioneering advocate for persons with circadian disorders.

Here is some of what Benjakob and Aviram wrote. (CC and CR refer to the wikipedia articles entitled “Circadian Clock” and “Circadian Rhythms”.)

The most prominent editor on the CR and CC
pages was a user called Hordaland, ranking first in
overall edits to these articles (244 in CR and 14 in CC),
(Fig. 3A). We successfully identified Hordaland as
Beth MacDonald, an American based in Norway who
had delayed sleep phase disorder (DSPS). MacDonald,
who died in 2017, maintained a blog in collaboration
with James Fadden, a biochemist working in private
industry who confirmed her identity to us. Together,
the two founded an international nonprofit called the
Circadian Sleep Disorder Network. In the sleep disorder
network’s blog, MacDonald wrote that her “mission
is to inform [people] about DSPS based on what
I’ve learned since diagnosis” (MacDonald and
Fadden, 2017). Describing MacDonald as someone
with both intimate and scientific knowledge of the
topic to which she contributed vastly online, Fadden
wrote, “Despite having no formal scientific training,
[MacDonald] steeped herself in the circadian science
literature.”

I need to add one point to that paragraph. Although Beth and I played important roles in helping The Circadian Sleep Disorders Network get started, the lions share of the organizational work (including the legal incorporation papers and setting up the web site) was done by Peter Mansbach, the founding president. I wrote to the authors to correct their ommision but by then the paper had already been published.

They made an interesting observation about the times of day when Beth did her editing.

Because every edit is logged, one could use editing
activity as a form of action metric (Yasseri et al.,
2012a). To get to know our main characters better, we
created actographs for their editing patterns in
Wikipedia: While Looie496 (Skaggs) edited in a
highly rhythmic daily cycle, Hordaland (McDonald),
who had a sleeping disorder, edited around the clock.
Gorton K, the purported “budding biologist,” edited
rather sporadically, mostly on Thursdays (Fig. 3C).

These graphs are remarkable in two ways. The bar graphs show the large quantity of edits by Beth (Hordaland). The spot graphs show the time of day when she made her edits. They show the imprint of her circadian disorder. She was mostly awake at night but could be awake at any time of day or night, in contrast to the other contributors who did not have a circadian disorder and whose edits were at more consistent times.

There is a discussion of the interaction of “citizen encyclopedists” and scientists in Wikipedia.

Among the CC and CR contributors, we identified
those whom we call “citizen encyclopedists,” like
Hordaland, who played a role that has historically
been reserved for academics…

As well, real-world scientists active in Wikipedia
also contributed, functioning as a specific kind of
reviewer who could be labeled a “scientific gatekeeper.”…

Reading through Wikipedia’s talk pages, we also
located interactions between these two different
types of authors (lay and expert). For example,
Hordaland periodically edited another article called
“Bacterial circadian rhythms,” which was opened by
a user identifying as Carl Hirschie Johnson, whom
we independently confirmed to be the clock scientist
from Vanderbilt University. Hordaland exemplifies
how despite Wikipedia’s lax admission standards, it
can attract a different kind of expert—a “lay expert”
(Prior, 2003)—with a personal and vested interest
who may or may not have formal academic training
but who maintains an ongoing dialogue with the relevant
scientific community. Indeed, Hordaland even
thanked Prof. Johnson for writing “a very interesting
article.”

In a telling example, after Hordaland changed the
opening section of the CR article to state that
“Circadian rhythms are endogenous and can be
entrained by external cues,” Looie496 wrote to her on
her talk page to say that the word “and” in the sentence
should be replaced with “but,” as the former
“seems confusing to me. . . . Given that circadian
rhythms are generated internally, it will be unexpected
that external cues control them, so the word
‘but’, is needed for clarity” (1744 h, 7 February 2010).
Hordaland responded cordially, offering an alternative
formulation, “hoping this reword[ing] satisfies
us both: ‘Although circadian rhythms are endogenous,
they are adjusted (entrained) to the environment
by external cues called zeitgebers, the primary
one of which is daylight’ ” (1831 h, 8 February 2010).
Looie496 agreed: “That works fine for me, thanks”
(2120 h, 8 February 2010).

These interchanges bring to light an encyclopedic
effort in which laypeople and experts not only write
different parts of the article but also edit it collaboratively.

You couldn’t mess with Wikipedia when Beth was on the case!

For example, a user called Brian Phosphorus made
the following edit to the article for “Circadian
rhythm” (CR) on May 17, 2008:

Circadian rhythms is a rapper from Peabody, Ma. He has yet
to release an album, but he performs many live shows from
his house/car. Born in 1985, CR has an older sister and a
younger brother, and two parents.

The example of the aspiring rapper shows how
people try to use the encyclopedia for self-promotion.
Tellingly, only 7 minutes later a user called Hordaland
deleted the rapper’s unremarkable biography from
the “Circadian rhythm” article, which more readily
defines circadian rhythms as “any biological process
that displays an endogenous, entrainable oscillation
of about 24 hours.”

While I have picked out the sections mentioning Beth’s work, the entire article is worth reading as a fascinating analysis of the cooperation of scientists and interested citizens in adding to the Wikipedia knowledge base. Personally, I have always had a particular interest in the history and philosophy of science, so this article appealed to me in many ways. I know Beth would have found it fascinating as well.

Congratulations to Omer Benjakob and Rona Aviram for an excellent article. Beth would have been proud of you.

1. Benjakob O, Aviram R. A Clockwork Wikipedia: From a Broad Perspective to a Case Study. J Biol Rhythms. 2018 Jun;33(3):233-244.

The article is freely available (three cheers for open access) for download as a pdf file. I highly recommend it.

http://journals.sagepub.com/doi/10.1177/0748730418768120

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N24 Awareness Day 2017: Through the Looking Glass

24 November 2017 at 07:34 | Posted in Body clock, Circadian rhythm, Clock genes, N24 | Leave a comment

I apologize if this year’s post is shorter than most. I am still recovering from a nasty case of the flu which has really drained my energy. But N24 Day must go on!

Many of you reading this post will have some idea of what N24, also known as Non-24 or Non-24-hour sleep-wake cycle disorder, consists of. But as the theme for today is awareness I will first start off with some links that explain the disorder.

I have written an article for Sleep Review entitled All You Need to Know about N24, which many patients and health professionals have found helpful. I also co-authored (with Dr Katherine Sharkey) a report on Non-24 for the the National Organization of Rare Disorders. Another excellent source of information on N24 and other circadian disorders is the Circadian Sleep Disorders Network. If you have a circadian disorder please take their survey.

The theme of this year’s N24 Awareness Day is Through the Looking Glass. This theme is meant to reflect the strange time-disordered world those of us with N24 find ourselves living in. Even Lewis Carroll did not imagine the strangeness of creatures living on a 25 or 26 or 30 hour cycle in a 24-hour world. (Although one may wonder if the White Rabbit was one of us, always running late and looking at his watch.)

But I want to talk about something that happened this year which may be a through-the-looking-glass moment for the science of circadian rhythms and the public awareness of the same. The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their discoveries of molecular mechanisms that control circadian rhythms.

Starting in the 1980s Hall, Robash and Young worked on the oscillation of proteins in the fruit fly and with an amazing amount of painstaking work over many years were able to draw a picture of what, in a biochemical sense, are the gears of the internal clock. The clock in mammals, such as humans, turns out, with some modifications, to work the same way as in fruit flies.

The basic model is that of the transcription-translation feedback loop. Regions of DNA are transcribed (copied into RNA) and then translated (the RNA is used to make protein). The proteins produced then act to control the transcription/translation process that produced them. As more of the end protein are produced signals are sent back to say, “make less protein” and so the level starts to fall again. A rise and fall of specific protein levels occurs in a rhythmic fashion, and numerous other loops of protein transcription/translation help to fine-tune this rise and fall so it occurs every 24 hours in a healthy organism.

The key protein in Hall and Robash’s early work was the PER (for period) protein. Young then discovered another gene/protein combination, the timeless gene producing TIM protein. Together these form the basic parts of the fruit fly clock (but many other parts are needed to make it work precisely). Other researchers then extended this work to mammalian (including human) clocks, discovering the roles of the CLOCK, CRY and other proteins.

This research has been going on for many years, so what I have been describing is not new. What is new is the decision of the Nobel Prize Committee to give this work the recognition it deserves. This is part of a trend–more and more papers at sleep conferences and other scientific societies now focus on circadian rhythms.

For too many scientists, doctors and members of the general public it has been tempting to think of circadian rhythms as something secondary, something superimposed on the basic functions of the body, but which one can generally ignore. This view is no longer tenable. The transcription-translation feedback loop that controls the circadian clock lives in the heart of every cell in the body, literally inscribed in the DNA that allows us to live. Those who pay attention have realized this for some time. But the Nobel prize is a bell in the dark, alerting the rest of the world to this fact.

Those of us with N24 are not the sole inhabitants of the mysterious beyond-the-looking glass realm of circadian rhythms. That realm is the inner sanctum of life itself. We live on a planet that spins every 24 hours and this is imprinted on our being.

This prize is not going to mean a sudden era of rainbows and sunshine for those of us with N24. It may be years before these discoveries will have practical impact on our condition. But this is nonetheless a big step. When we say to our doctors or families or others that we have a circadian disorder, we can know that the Nobel Prize committee has told the world, in no uncertain terms, that circadian rhythms are real, they are important, and to them attention must be paid.

James Fadden

Sad News

11 August 2017 at 04:53 | Posted in Circadian rhythm | 9 Comments

I have some very sad news. Beth MacDonald, also known as delayed2sleep, the founder and co-author of this blog, has passed away.

Beth had suffered from DSPS since childhood. As an adult she worked for many years as a school teacher, one of the most lark-oriented professions. On only a few hours of sleep she would force herself get up early to work, making up for it with a long nap in the early evening. For most of her life she did not know of the existence of DSPS. But when finally diagnosed, she made it her life mission to be sure that no one would have to struggle in the way she did.

She was for many years one of the most prolific and helpful posters on the Nite Owl mailing list. Despite having no formal scientific training, she steeped herself in the circadian science literature. In 2005 she started this blog, which she asked me to join as co-blogger in 2010. Starting in 2007 she was very active in editing the Wikipedia articles on circadian disorders. In 2011 she became one of the founding members of the Circadian Sleep Disorders Network, a patient support and advocacy organization, where she served for many years as secretary. She was also very active in the Facebook circadian groups (as Nina Beth) and on other online venues.

A someone put it the other day, Beth was the “heart and soul” of the online circadian disorders community. She was unfailingly generous with her time and energy. In my experience she was one of the kindest and nicest people I have ever met. I think I can speak for the whole community in saying she will be terrible missed.

In recent years Beth and I have focused a lot of our energy towards helping the work of CSD-N, so posts on this blog have been less frequent, although still appearing on occasion. It has been a source of happiness for both of us that so many people have found this blog to be useful. People have often told us that this was the first place where they learned that their sleep problems were due to a real disorder.

I should note that when posting on this blog, Beth maintained her anonymity, posting as delayed2sleep (or just “D”). I had to do some serious thinking about whether to break that anonymity. But in the past few years she had told me she was thinking of using her own name, as she did on CSD-N and in her other advocacy work. So I felt it appropriate to use her real name here. At the very least, she deserves to be known for the good work she has done.

I have been pacing back and forth for a good half hour hesitating to press “publish” on this post. Partly, it’s the finality of it. But there is something else, which, if Beth were here, she’d get a good chuckle out of. You see, Beth was an amazing proofreader. If you wanted something checked over for a misplaced comma or a dangling participle, you’d ask Beth. And I am sure this post has a few mistakes that could use Beth’s eagle eye. But as hard as she was on her own mistakes, she was always forgiving of the mistakes of others. So I’m not going to worry.

I do plan to continue this blog. Due to my CSD-N work and other obligations, posts may not be frequent, but I will try to post when possible, sometimes cross-posting on CSD-N. For certain, the blog will remain up as long as I am around.

And with that, I will press “publish”.

Farewell, Beth, my co-blogger and my friend.

James Fadden (aka LivingWithN24)

N24 Awareness Day 2016: Genetics, the new face of N24 and DSPS.

23 November 2016 at 05:26 | Posted in Body clock, Circadian rhythm, Clock genes, DSPS, N24 | 4 Comments

I got my genes tested this month, and what I found out puts a new face on my understanding of N24 and DSPD.

faces2

The first human genome was sequenced in 2003 and cost 2.7 billion dollars.  Over the years researchers have improved their technique and reduced the cost dramatically.  Recently Veritas Genetics announced it had reached the goal of the under $1000 genome, offering a full genome sequence to anyone for $999.  Still very expensive but quite a drop from 2.7 billion!

Other companies also offer a more limited but still useful form of genomic testing.  One of these is 23andMe which offers testing for $99-$199.  Rather than plunging into the deep end  of whole genome sequencing, I thought I’d go with 23andMe to confirm that I could get useful information with less expense.  I am very impressed with what I was able to find out from 23andMe.

The method of 23andMe is based on analysis of what are called single nucleotide polymorphisms (SNPs).   Most of the human genome is identical from person to person, which is why we are all humans and not horses or banana trees.  SNP analysis focuses on variations in the genome of a particular common type.

The genetic code is a sequence of DNA nucleotides which we label with the letters A,T,G or C.   So part of the code might read like this: …CTGAATGCAGT…  An SNP refers to a situation where one letter of the code differs from person to person.   So while one person may have the sequence CTGAATGCAGT  another may have the sequence CTGAATTCAGT.   Notice the only change is that the letter G in the 7th place has become a T.   Typically one SNP will be more common in the population than the other.  So, for example 90% of the population may have a G, which would be referred to as the major (more common) allele.   The T would be called the minor allele.  (Allele is another word for genetic letters.)

So if you sign up for 23andMe you send them a vial of your spit, and 4-6 weeks later they send you a link to their site where they give you information about a selection of your SNPs and what they mean, as well as some other genetic information.

Most of the information you get from 23andMe, at first glance, seems pretty basic.  They tell you where your ancestors came from and a list of various genetic traits: is your hair likely to be curly, can you taste bitter foods etc.  Interesting but hardly world-shaking in most cases.

But in addition to this pre-analyzed information 23andMe also allows you to download a file containing the raw data: a long list of the actual SNPs and your results.   These you can upload to certain web sites such as Promethease for detailed analysis, or if you know what you are doing and what you are looking for you can look through the raw data yourself.  That’s when the fun begins.

And I knew just what I wanted to look for.

In 2014 Daniel Kripke et al. published an article called, Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles.  You can get the full text at the link below.

https://synapse.koreamed.org/DOIx.php?id=10.4306/pi.2014.11.4.345

The study identified several SNPs statistically associated with N24 or DSPS.   Not all of the SNPs studied by Kripke et al were tested by 23andMe but three of the most important ones were.

In the case of N24, Kripke et al. were particularly interested in variations in a gene called BHLHE40, or basic helix-loop-helix protein E 40.   The protein produced by this gene plays a major role in the molecular clock.

http://www.uniprot.org/uniprot/O14503

The study found that subjects with N24 were statistically more likely to have one or two C alleles instead of a T at a portion of the genome labelled rs908078, which is part of the regulatory sequence for this gene.   Looking at my 23andMe data I found this line:

rs908078        3       5024771 CT

So, yes indeed I did have one C allele.  It might have been even more impressive if I had two, as some of the N24 subjects did, but one C is still interesting.

But I developed N24 as an adult, following chronotherapy. Before that I had DSPD.  So if there is a genetic predisposition it might be even more likely to show up in genes associated with DSPD.  Kripke et al found two such genes and corresponding SNPS.

The first is a gene called NFIL3 (nuclear factor, interleukin 3 regulated).  It also plays a role in the circadian clock.

https://www.ncbi.nlm.nih.gov/gene/4783

The SNP for NFIL3 is rs2482705, and people with DSPS are more likely to have two G alleles. So looking at my data file I find this line.

rs2482705       9       94182502        GG

So, yes, GG.  I can cross out another letter on my bingo card.

The other gene is RORC (retinoic acid receptor-related orphan receptor C).  This gene has many functions and is not well understood, but one of its roles is also in clock regulation.

http://www.genecards.org/cgi-bin/carddisp.pl?gene=RORC

The associated SNP is designated rs3828057.  People with DSPS are more likely to have a GG allele.  Going back to my data file I search for that string and find this.

rs3828057       1       151780177       CC

You might at first think that was a miss, but remember the structure of DNA.  It consists of two strands linked together in a helix, which run in opposite directions, the sense strand and the antisense strand.   A C in the sense strand matches a G in the antisense strand, and vice versa.  An A matches to a T.  So CC is actually equivalent to a GG in this case.  It simply means one group tested the sense strand and the other the antisense strand.

So we have another hit.

So for the SNPs that were tested  by 23andMe I am 3 for 3 in having the alleles associated with N24 or DSPD.  I don’t want to make too much of this.   These are statistical associations.  It’s entirely possible to have either disorder and not have these genes or to have the genes and not the disorder.  Nonetheless, while I am not yet ready to shout BINGO!,  I find the presence of these genes intriguing.  We aren’t quite ready to trace their function directly to the disorder but that may come in time. The first step in that process is to know what genes are involved. The fact that these genes are ones we do know are intimately involved in regulating the circadian clock is a good omen for our future understanding.

But there is also more on the horizon.  Recall I mentioned 23andMe only tests a limited number of SNPs.   Kripke et al reported a total of 9 SNPs associated with N24.  While rs908078 was the one they focused on the most, the other 8 are also significant.  But 23andMe only tested for rs980078.  They did not test the other 8.  But a whole genome sequencing, if I am ever able to afford that, should give results for the other 8. That’s a lot more letters to put on the bingo card!

I don’t think we are likely to explain N24 or DSPD entirely based on genetics.  Developmental and epigenetic factors almost certainly play a role.  But the more we know about the genetic aspects, the better off we will be. I must also add that genetic studies are not always replicated and it may turn out that all of this is a Will-o’-the-wisp that I will have to retract next year.  But eventually real data will come out.  As one of my favorite fictional characters said, “the truth is out there.”

LivingWithN24 (James Fadden)

This post also appears on the CSD-N web site.  Please join CSD-N to help support research like this.

72. 2015 in review

20 May 2016 at 12:38 | Posted in Circadian rhythm | Leave a comment

The WordPress.com stats helper monkeys prepared a 2015 annual report for this blog.

Here’s an excerpt:

The concert hall at the Sydney Opera House holds 2,700 people. This blog was viewed about 24,000 times in 2015. If it were a concert at Sydney Opera House, it would take about 9 sold-out performances for that many people to see it.

Click here to see the complete report.

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