Category Archives: Medicine

Books: ‘The Poisoner’s Handbook’ by Deborah Blum

Poisoner's Handbook cover.jpgIf you picked up The Poisoner’s Handbook (amazon.com) looking for a fool-proof recipe, I hope you have read the book through and realized at the end that such a thing does not exist: you’ll get busted. If they could figure it all out back in 1930s, can you imagine how much easier they can figure out a case of poisoning today, with modern sensitive techniques? And if you have read the book through, I hope you found it as fascinating as I did. Perhaps you should use your fascination with poisons to do good instead, perhaps become a forensic toxicologist?
My SciBling Deborah Blum (blog, Twitter) has done it again – written a fast-paced page-turner, full of action and intrigue, and with TONS of science in it. It reads like a detective novel. Oh, wait, it is a detective novel. Who said that an author has to invent a fictional detective, an Arsene Lupin or Hercule Poirot or Sherlock Holmes or the Three Investigators? There existed in history real people just like them, including Charles Norris and Alexander Gettler, the heroes of The Poisoner’s Handbook.
Charles Norris was the first Chief Medical Examiner of the City of New York, or at least the first one who was actually qualified for that position which, before him, was a political appointment not requiring any expertise. Norris served in this role from 1918. to 1935. and revolutionized both the position and the science of forensic medicine. Alexander Gettler was one of his first appointees, who served as New York City’s chief toxicologist until 1959.
The two of them used their prominent position to set the new high standards for the profession of a public medical examiner, and also set the new high standards for the scientific research in forensic pathology, including forensic toxicology – the study of the way poisons kill and how to detect it. They affected rules and legislation with their work, they sent clever murderers to the electric chair, and exonerated the innocents who were headed that way due to mistakes of the non-science-based courtroom battles. And in order to do that, they needed to do a lot of their own research during many years of long days and nights in the lab performing meticulous and often gruesome studies of the effects of various substances on animals, people, living and dead tissues and coming up with ever more sensitive and clever methods for detecting as small quantities of the poison as was technically possible at the time.
In the author’s note at the end of the book, Deborah Blum notes that there were many other forensic scientists before, during and after the Norris-Gettner era, and many of them got mentioned in the book or are cited in the EndNotes (which I discovered only once I finished the book – I hate the way publishers do this these days!). But it is also true that Norris and Gettner were the leaders – they used their prominent position and political clout, and their meticulous research defined the high standards for the nascent discipline. In a way, the central importance and prominence of these two men worked well for the book – here we have two interesting characters to like and follow instead of a whole plethora of unfleshed names. And as each chapter focuses on one poisonous substance and one or two notorious cases of its use, it is just like following Holmes and Watson through a series of Sir Arthur Conan Doyle’s stories – the two characters are the connecting thread, and they evolve throughout their lives and throughout the book, case by case.
Apart from being a history of forensic toxicology, the book has several other themes that keep recurring in each chapter, as they chronologically unfold. The book is also a history of 1920/30s New York City, and a history of technology and engineering. Carbon monoxide poisoning? That was the beginning of the car craze. Gas? Everyone cooked and heated with it at the time. Some other poisons were easily found in many over-the-counter products in stores and pharmacies.
Having just read On The Grid, I was also attuned to the discussions of infrastructure of NYC in the early 20th century. How did people transport themselves? Air pollution? Gas? Clean water? Wastewater? All sources of potentially toxic chemicals. How efficient was garbage collection? Not much….thus there were many rats. And rats needed to be controlled. And for that, there was plenty of rat poison to be bought. And rat poison can kill a human as well – inadvertently, as a method for suicide, or as a murder weapon. It is kinda fun to see some of the same infrastructure issues, like garbage disposal and pest extermination in N.Y.City, addressed from different angles in different books – this one, On The Grid, as well as Rats, another fascinating science book that covers New York City engineering, infrastructure and politics of the time. All the threads tie in together….
Another topic addressed in each chapter was Prohibition. One can certainly die of a huge overdose of ethyl alcohol normally found in drinks, but at the time when producing and selling drinks was illegal, people still drank, perhaps even more. And what did they drink? Whatever they could find on the black market – home-made concoctions brewed by unsavory types more interested in profit than the safety of their product. Instead of ethyl, those drinks were mostly made of methyl (wood) alcohol which is much more dangerous in much smaller doses. Prohibition saw a large increase in drinking-related deaths, a fact often loudly pronounced by Norris, leading to the eventual end of Prohibition. Can we apply that thinking to the War On Drugs now?
And the story of Prohibition has another element to it – the importance of regulation. An unregulated substance is potentially dangerous. By solving a number of poisoning cases, and by doing their research on the toxicity of then easily available substances, Norris and Gettner have managed to initiate regulation of a number of toxins, or even their removal from the market altogether. Some substances that were found in everything, even touted as health potions (even radioactive substances!!!) were discovered by forensic toxicologists to be deadly, and were subsequently banned or rigorously controlled. Today we have entire federal agencies dealing with regulation of dangerous chemicals, but in the early 20th century, it was the time of laissez-faire murder, suicide, suffering and death.
Finally, after I finished this fascinating book, I realized it gave me something more: an anchor, or a scaffolding, or a context, for every story about poisons I see now. Now every blog post on Deborah’s blog makes more sense – I can fit it into a body of knowledge and understanding I would not have if I have not read the book. This really goes hand in hand with the recent discussions of #futureofcontext in journalism – see The Future Of Context for starters. The idea is that news stories do not provide enough context for readers who tune into a new topic for the first time. A story that is an update on an ongoing story is not comprehensible without some context, which the news story cannot provide. So now various media organizations are experimenting with ways to provide context for people who are just tuning in. The perfect source of context for a topic is a book, especially now that every book appears to have its own website with links and news and a blog and a Twitter feed and a Facebook page. The book provides context, and all these other things provide updates.
For example, reading Bonobo Handshake may not provide much more context for me about animal behavior and cognition since I already have that context, but it certainly now makes it easier for me to understand the news stories regarding conservation of great apes. And without that book I would never have sufficient background in the recent history of Congo to understand and appreciate this comment thread. ‘On The Grid’ gives me context for all news regarding infrastructure. Explaining Research is a great recent example of a book that is a great start on the topic, but which constantly reminds the reader that this field is in flux and that the book’s website contains frequent updates and additional resources. The Immortal Life of Henrietta Lacks provides fantastic context for the discussions of medical ethics and its evolution in the USA in the past several decades, which I riffed off a little bit in my latest interview.
What reading The Poisoner’s Handbook did for me is to give me enough knowledge and understanding on the topic that I can really appreciate it. I now get excited about news stories regarding poisons because I feel I understand them better. While reading Deborah Blum’s blog was interesting before, now it is more than interesting – it is exciting and I can’t wait for a new post to show up. I did not know how much I did not know. Now that I do, I want to know more. I am hungry for more knowledge, and more news, and more stories about toxins and poisons and how various strange and not so strange substances affect our bodies – where they come from, how they get in, how they hijack or disrupt our normal biochemical processes, how they kill us, and how do we figure that all out in the laboratory or in the basement of the mortuary. I hope you will feel the same once you finish reading this book. You will do that now, OK?

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The Benefits and Burdens of Genetic Testing

New podcast and forums at World Science: The Benefits and Burdens of Genetic Testing:

Listen to a story by reporter Marina Giovannelli, followed by our interview with Mayana Zatz.
Download MP3
Our guest in the Science Forum is geneticist and genetic counselor Mayana Zatz. She directs the Human Genome Research Center at the University of Sao Paolo.
Zatz has been working with patients with inherited disorders for nearly two decades. When it comes to genetic testing, Zatz advocates caution. Tests for some inherited disorders have helped people decide whether or not to have children. But in most cases, Zatz says genetic testing raises complex psychological and ethical issues:
* Should children be tested for late-onset disorders like Huntington’s disease and cerebellar ataxia? Doing so could lead to a life of dread, as they wait for a disease for which there is no cure.
* Interpreting the results from a genetic test can be difficult, especially for complex diseases like cancer or Alzheimer’s which are triggered by multiple factors, not just genetics.
Come join the conversation with Mayana Zatz. She’s taking your comments and questions through July 13th.
* Have you had your genes read? How did the results change your life?
* Should companies offering such tests be regulated?
* What kinds of medical benefits can we expect from genomics research in the coming years?

Real Guys Immunize

guyzimmunize logo.jpgLast week I went to Philadelphia to a very interesting meeting – a Social Media Summit on Immunization. Sponsored by Immunization Action Coalition, this was a second annual meeting for health-care non-profits, organized (amazingly well, with great attention to detail) by Lisa Randall (and, I am sure, a small army of helpers).
Over a day and a half of the meeting there were two simultaneous sessions at each time slot, but I did not have much opportunity to ponder my choices as I was at the front of the room at three sessions, and participated actively in several others. The style was very ‘unconference-y’, with barely any PowerPoint – we talked and showed stuff on the Web as needed.
We discussed pros and cons of using various online platforms for spreading the message about vaccinations (which also means pushing back against anti-vaccination propaganda), making sure that all of the representatives of the non-profits understand they don’t have to use all (or any) of them unless this can be useful for the work they want to do and the goal they want to achieve. But if they do feel it is necessary, we were there to explain and demonstrate how to do it: static pages, blogs, Facebook, Twitter, YouTube, etc., the best practices and strategies for using each of these platforms, the metrics for measuring the spread of their message, etc. This was a LOT of stuff, and we covered a lot of ground, but I hope we were useful.
On the second day, we had a very interesting discussion following the presentation by Anna Kata, anthropologist from McMaster University, whose recent paper, A postmodern Pandora’s box: anti-vaccination misinformation on the Internet, analyzed the arguments by the anti-vaccination groups use in their online discussions. What is most interesting is that every single one of these arguments is nothing new – each has been used from the very beginning of vaccination, in 1796, from personal attacks on Edward Jenner, to arguments about “playing God”, to fear of putting animal material into bodies, to suspecting a conspiracy by government, industry and medical profession, to arguments for personal freedom, to proposing alternative theories of health (and disease and treatments). It never really stopped, it just has some very prominent spokesemen right now, visible in the media.
What is important is that people who reject vaccination are not the uneducated and the poor. The poor tend to trust the authority of physicians and will gladly vaccinate – if they can afford it. It is the upper-middle-class, at least nominally well educated, that refuses to vaccinate their kids. Trying to change their minds by presenting them the information does not work – they do not treat that information as valid. They live in a post-modern world in which everyone is entitled to their own facts. Their notions of body, health, and disease are very holistic, very New-Agey, so medical information does not mean anything to them. But they (not the activists, but parents seeking information) can be swayed by peer pressure. And nothing works better than for them to hear, from their friends, family, neighbors, colleagues and physicians, over and over again “I vaccinated my kids, trust me, I know what I’m doing, you should vaccinate yours, too.” If people they trust vaccinate, they will start wavering in their beliefs and may end up vaccinating themselves in the end. It is that social pressure, and need to socially conform, that is much more powerful than all the medical information in the world.
As a demonstration of the way, and ease of the way, for putting together a social media strategy, a group of ‘Social Media Ninjas’, about 5-6 of them who have never met or worked together before, took over one of the rooms and all of its computers during the meeting. They had 24 hours from start to finish. They started by crowdsourcing ideas, then picking one and running with it. The one they picked was focused on explaining ‘herd immunity’ and the target audience was men.
Almost all of the activity in persuading people to vaccinate their kids targets women, as it is supposed that mothers are the only ones making decisions about their children. This leaves out half of the population. And that half of the population can really help. In some families, still in the 21st century I know, the father has the last word. In other families, mother may resist vaccines out of fear and insecurity and her husband’s support can make all the difference – they can study the issue together, discuss it and make the decision together.
So the Social Media Ninja team, in that 24-hour period, came up with the name – “Real Guys Immunize” – drew a logo, and built a static web page, which explains what this is all about, provides brief FAQs and links to external resources. It also provides an easy way for readers to post personal stories.
They started a Twitter account (and the #guysimmunize hashtag), a YouTube channel and a Facebook page. They designed an e-card for Father’s Day. They had a couple of participants write blog posts (see here and here). And they put together a cool slideshow:

They decided against making a video (24 hours was too short, and nobody in the room was a real video-maven) though this can be done later, and made other changes to the original plan as the 24 hours passed. At the very end, they presented all of that to the gathering, including the first metrics of their reach (whatever one can measure after such a short time):

The site (and everything else associated with it on social media) is not really owned by anyone – it was just an experiment done to show how such a thing is made. So, if anyone is interesting in taking over this initiative and moving it forward into the future, there is a contact e-mail there, just click.

Going Mad The American Way

New podcast and forum at PRI World Science:

Listen to a story by reporter Laura Starecheski, followed by our interview with Ethan Watters.
Our guest in the Science Forum is journalist Ethan Watters.
His latest book is Crazy Like Us: The Globalization of the American Psyche.
“America is homogenizing the way the world goes mad,” Watters writes. He contends that Americans are exporting their view of mental illness to the rest of the world.
Watters says culture influences not only how people deal with mental disorders but how mental disorders manifest themselves. Yet those cultural differences are disappearing as Western notions of mental health become popular worldwide.
Some examples Watters cites in his book:
• Anorexia nervosa, the eating disorder, is now common in countries with no history of the disease.
• Modern biomedical notions of schizophrenia are replacing the idea of spirit possession in places like Zanzibar.
• By selling pills for depression, pharmaceutical companies have caused a rise in the diagnosis of depression in Japan.
Bring your thoughts and questions about culture and mental illness to Watters. The discussion is just to the right.
* Is America’s view of mental health reflective of the nation’s individualistic culture?
* Have you or a family member been diagnosed with mental illness? Has your ethnic or religious background influenced your response?
* Would Americans benefit from importing ideas of mental health from other countries?

Related reading: The Americanization of Mental Illness.

Public vs. Publicized: Future of the Web at WWW2010

2010-logo-small1.jpgIt is somewhat hard to grok how much a Big Deal the WWW2010 conference is when it’s happening in one’s own backyard. After all, all I had to do was drop the kids at school a little earlier each morning and drive down to Raleigh, through the familiar downtown streets, park in a familiar parking lot, and enter a familiar convention center, just to immediately bump into familiar people – the ‘home team’ of people I have been seeing at blogger meetups, tweetups and other events for years, like Paul Jones, Ruby Sinreich, Fred Stutzman, Ryan Boyles, Wayne Sutton, Kim Ashley, Henry Copeland and others.
But it is a Big Deal. It is the ‘official’ conference of the World Wide Web. Yup, Tim Berners-Lee, the guy who invented the Web, was there. I saw him, though I did not talk to him. I mean, what excuse could I come up with to approach him? Ask him to autograph my web browser?

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A new medical research blog

Introducing Beaker, inspired by our panel at AAAS a couple of months ago. Go take a look.

Evolutionary Medicine: Does reindeer have a circadian stop-watch instead of a clock?

ResearchBlogging.orgWhenever I read a paper from Karl-Arne Stokkan’s lab, and I have read every one of them, no matter how dense the scientese language I always start imagining them running around the cold, dark Arctic, wielding enormous butterfly nets, looking for and catching reindeer (or ptarmigans, whichever animal the paper is about) to do their research.

Reindeer_bw.GIFlepidopterist.gif

If I was not so averse to cold, I’d think this would be the best career in science ever!
It is no surprise that their latest paper – A Circadian Clock Is Not Required in an Arctic Mammal (press release) – was widely covered by the media, both traditional and blogs, See, for example, The Scientist, BBC, Scientific American podcast and Wired Science.
Relevant, or just cool?
It is hard to find a science story that is more obviously in the “that’s cool” category, as opposed to the “that’s relevant” category. For the background on this debate, please read Ed Yong, David Dobbs, DeLene Beeland, Colin Schultz, and the series of Colin’s interviews with Carl Zimmer, Nicola Jones, David Dobbs, Jay Ingram, Ferris Jabr, Ed Yong and Ed Yong again.
I agree, it is a cool story. It is an attention-grabbing, nifty story about charismatic megafauna living in a strange wilderness. I first saw the work from the lab in a poster session at a conference many years ago, and of all the posters I saw that day, it is the reindeer one that I still remember after all these years.
Yet, the coolness of the story should not hide the fact that this research is also very relevant – both to the understanding of evolution and to human medicine. Let me try to explain what they did and why that is much more important than what a quick glance at the headlines may suggest. I did it only part-way a few years ago when I blogged about one of their earlier papers. But let me start with that earlier paper as background, for context.
Rhythms of Behavior
In their 2005 Nature paper (which was really just a tiny subset of a much longer, detailed paper they published elsewhere a couple of years later), Stokkan and colleagues used radiotelemetry to continuously monitor activity of reindeer – when they sleep and when they roam around foraging.
You should remember that up in the Arctic the summer is essentially one single day that lasts several months, while the winter is a continuous night that lasts several months. During these long periods of constant illumination, reindeer did not show rhythms in activity – they moved around and rested in bouts and bursts, at almost unpredictable times of “day”. Their circadian rhythms of behavior were gone.
But, during brief periods of spring and fall, during which there are 24-hour light-dark cycles of day and night, the reindeer (on the northern end of the mainland Norway, but not the population living even further north on Svaldbard which remained arrhythmic throughout), showed daily rhythms of activity, suggesting that this species may possess a circadian clock.
Rhythms of Physiology
In a couple of studies, including the latest one, the lab also looked into a physiological rhythm – that of melatonin synthesis and secretion by the pineal gland. Just as in activity rhythms, melatonin concentrations in the blood showed a daily (24-hour) rhythm only during the brief periods of spring and fall. Furthermore, in the latest paper, they kept three reindeer indoors for a couple of days, in light-tight stalls, and exposed them to 2.5-hour-long periods of darkness during the normal light phase of the day. Each such ‘dark pulse’ resulted in a sharp rise of blood melatonin, followed by just as abrupt elimination of melatonin as soon as the lights went back on.
reindeer melatonin.jpg
Rhythms of gene expression
Finally, in this latest paper, they also looked at the expression of two of the core clock genes in fibroblasts kept in vitro (in a dish). Fibroblasts are connective tissue cells found all around the body, probably taken out of reindeer by biopsy. In other mammals, e.g., in rodents, clock genes continue to cycle with a circadian period for a very long time in a dish. Yet, the reindeer fibroblasts, after a couple of very weak oscillations that were roughly in the circadian range, decayed into complete arrhytmicity – the cells were healthy, but their clocks were not ticking any more.
reindeer fibroblasts.jpg
What do these results suggest?
There is something fishy about the reindeer clock. It is not working the same way it does in other mammals studied to date. For example, seals and humans living in the Arctic have normal circadian rhythms of melatonin. Some other animals show daily rhythms in behavior. But in reindeer, rhythms in behavior and melatonin can be seen only if the environment is rhythmic as well. In constant light conditions, it appears that the clock is not working. But, is it? How do we know?
During the long winter night and the long summer day, the behavior of reindeer is not completely random. It is in bouts which show some regularity – these are ultradian rhythms with the period much shorter than 24 hours. If the clock is not working in reindeer, i.e., if there is no clock in this species, then the ultradian rhythms would persist during spring and fall as well. Yet we see circadian rhythms during these seasons – there is an underlying clock there which can be entrained to a 24-hour light-dark cycle.
This argues for the notion that the deer’s circadian clock, unless forced into synchrony by a 24 external cycle, undergoes something called frequency demultiplication. The idea is that the underlying cellular clock runs with a 24-hour period but that is sends signals downstream of the clock, triggering phenotypic (observable) events, several times during each cycle. The events happen always at the same phases of the cycle, and are usually happening every 12 or 8 or 6 or 4 or 3 or 2 or 1 hours – the divisors of 24. Likewise, the clock can trigger the event only every other cycle, resulting in a 48-hour period of the observable behavior.
If we forget for a moment the metaphor of the clock and think instead of a Player Piano, it is like the contraption plays the note G several times per cycle, always at the same moments during each cycle, but there is no need to limit each note to appear only once per cycle.
On the other hand, both the activity and melatonin rhythms appear to be driven directly by light and dark – like a stop-watch. In circadian parlance this is called an “hourglass clock” – an environmental trigger is needed to turn it over so it can start measuring time all over again. Dawn and dusk appear to directly stop and start the behavioral activity, and onset of dark stimulates while onset of light inhibits secretion of melatonin. An “hourglass clock” is an extreme example of a circadian clock with a very low amplitude.
While we mostly pay attention to period and phase, we should not forget that amplitude is important. Yes, amplitude is important. It determines how easy it is for the environmental cue to reset the clock to a new phase – lower the amplitude of the clock, easier it is to shift. In a very low-amplitude oscillator, onset of light (or dark) can instantly reset the clock to Phase Zero and start timing all over again – an “hourglass” behavior.
The molecular study of the reindeer fibroblasts also suggests a low-amplitude clock – there are a couple of weak oscillations to be seen before the rhythm goes away completely.
There may be other explanations for the observed data, e.g., masking (direct effect of light on behavior bypassing the clock) or relative coordination (weak and transient entrainment) but let’s not get too bogged down in arcane circadiana right now. For now, let’s say that the reindeer clock exists, that it is a very low-amplitude clock which entrains readily and immediately to light-dark cycles, while it fragments or demultiplies in long periods of constant conditions.
Why is this important to the reindeer?
During long night of the winter and the long day of the summer it does not make sense for the reindeer to behave in 24-hour cycles. Their internal drive to do so, driven by the clock, should be overpowered by the need to be flexible – in such a harsh environment, behavior needs to be opportunistic – if there’s a predator in sight: move away. If there is food in sight – go get it. If you are full and there is no danger, this is a good time to take a nap. One way to accomplish this is to de-couple the behavior from the clock. The other strategy is to have a clock that is very permissive to such opportunistic behavior – a very low-amplitude clock.
But why have clock at all?
Stokkan and colleagues stress that the day-night cycles in spring help reindeer time seasonal events, most importantly breeding. The calves/fawns should be born when the weather is the nicest and the food most plentiful. The reindeer use those few weeks of spring (and fall) to measure daylength (photoperiod) and thus time their seasonality – or in other words, to reset their internal calendar: the circannual clock.
But, what does it all mean?
All of the above deals only with one of the two hypotheses for the adaptive function (and thus evolution) of the circadian clock. This is the External Synchronization hypothesis. This means that it is adaptive for an organism to be synchronized (in its biochemistry, physiology and behavior) with the external environment – to sleep when it is safe to do so, to eat at times when it will be undisturbed, etc. In the case of reindeer, since there are no daily cycles in the environment for the most of the year, there is no adaptive value in keeping a 24-hour rhythm in behavior, so none is observed. But since Arctic is highly seasonal, and since the circadian clock, through daylength measurement (photoperiodism) times seasonal events, the clock is retained as an adaptive structure.
This is not so new – such things have been observed in cave animals, as well as in social insects.
What the paper does not address is the other hypothesis – the Internal Synchronization hypothesis for the existence of the circadian clock – to synchronize internal events. So a target cell does not need to keep producing (and wasting energy) to produce a hormone receptor except at the time when the endocrine gland is secreting the hormone. It is a way for the body to temporally divide potentially conflicting physiological functions so those that need to coincide do so, and those that conflict with each other are separated in time – do not occur simultaneously. In this hypothesis, the clock is the Coordination Center of all the physiological processes. Even if there is no cycle in the environment to adapt to, the clock is a necessity and will be retained no matter what for this internal function, though the period now need not be close to 24 hours any more.
What can be done next?
Unfortunately, reindeer are not fruitflies or mice or rats. They are not endangered (as far as I know), but they are not easy to keep in the laboratory in large numbers in ideal, controlled conditions, for long periods of time.
Out in the field, one is limited as to what one can do. The only output of the clock that can be monitored long-term in the field is gross locomotor activity. Yet, while easiest to do, this is probably the least reliable indicator of the workings of the clock. Behavior is too flexible and malleable, too susceptible to “masking” by direct effects of the environment (e.g., weather, predators, etc,). And measurement of just gross locomotor activity does not tell us which specific behaviors the animals are engaged in.
It would be so nice if a bunch of reindeer could be brought into a lab and placed under controlled lighting conditions for a year at a time. One could, first, monitor several different specific behaviors. For example, if feeding, drinking and defecation are rhythmic, that would suggest that the entire digestive system is under circadian control: the stomach, liver, pancreas, intestine and all of their enzymes. Likewise with drinking and urination – they can be indirect indicators of the rhytmicity of the kidneys and the rest of the excretory system.
In a lab, one could also continuously monitor some physiological parameters with simple, non-invasive techniques. One could, for example monitor body temperature, blood pressure and heart-rate, much more reliable markers of circadian output. One could also take more frequent blood samples (these are large animals, they can take it) and measure a whole plethora of hormones along with melatonin, e.g., cortisol, thyroid hormones, progesterone, estrogen, testosterone, etc (also useful for measuring seasonal responses). One could measure metabolites in urine and feces and also gain some insight into rhythms of the internal biochemistry and physiology. All of that with no surgery and no discomfort to the animals.
Then one can place reindeer in constant darkness and see if all these rhythms persist or decay over time. Then one can make a PhaseResponse Curve and thus test the amplitude of the underlying oscillator (or do that with entrainment to T-cycles, if you have been clicking on links all along, you’ll know what I’m talking about). One can test their reproductive response to photoperiod this way as well.
Finally, fibroblasts are peripheral cells. One cannot expect the group to dissect suprachiasmatic nuclei out of reindeer to check the state of the master pacemaker itself. And in a case of such a damped circadian system, testing a peripheral clock may not be very informative. Better fibroblasts than nothing, but there are big caveats about using them.
Remember that the circadian system is distributed all around the body, with each cell containing a molecular clock, but only the pacemaker cells in the suprachiasmatic nucleus are acting as a network. In a circadian system like the one in reindeer, where the system is low-amplitude to begin with, it is almost expected that peripheral clocks taken out of the body and isolated in a dish will not be able to sustain rhythms for very long. Yet those same cells, while inside of the body, may be perfectly rhythmic as a part of the ensemble of all the body cells, each sending entraining signals to the others every day, thus the entire system as a whole working quite well as a body-wide circadian clock. This can be monitored in real-time in transgenic mice, but the technology to do that in reindeer is still some years away.
Finally, one could test a hypothesis that the reindeer clock undergoes seasonal changes in its organization at the molecular level by comparing the performance of fibroblasts (and perhaps some other peripheral cells) taken out of animals at different times of year.
What’s up with this being medically relevant?
But why is all this important? Why is work on mice not sufficient and one needs to pay attention to a strange laboratory animal model like reindeer?
First, unlike rodents, reindeer is a large, mostly diurnal animal. Just like us.
a1 reindeer.jpg
Second, reindeer normally live in conditions that make people sick, yet they remain just fine, thank you. How do they do that?
Even humans who don’t live above the Arctic Circle (or in the Antarctica), tend to live in a 24-hour society with both light and social cues messing up with our internal rhythms.
We have complex circadian systems that are easy to get out of whack. We work night-shifts and rotating shifts and fly around the globe getting jet-lagged. Jet-lag is not desynchronization between the clock and the environment, it is internal desynchronization between all the cellular clocks in our bodies.
In the state of almost permanent jet-lag that many of us live in, a lot of things go wrong. We get sleeping disorders, eating disorders, obesity, compromised immunity leading to cancer, problems with reproduction, increase in psychiatric problems, the Seasonal Affective Disorder, prevalence of stomach ulcers and breast cancer in night-shift nurses, etc.
Why do we get all that and reindeer don’t? What is the trick they evolved to stay healthy in conditions that drive us insane and sick? Can we learn their trick, adopt it for our own medical practice, and use it? Those are kinds of things that a mouse and a rat cannot provide answers to, but reindeer can. I can’t think of another animal species that can do that for us. Which is why I am glad that Stokkan and friends are chasing reindeer with enormous butterfly nets across Arctic wasteland in the darkness of winter 😉
Lu, W., Meng, Q., Tyler, N., Stokkan, K., & Loudon, A. (2010). A Circadian Clock Is Not Required in an Arctic Mammal Current Biology, 20 (6), 533-537 DOI: 10.1016/j.cub.2010.01.042