2017 Nobel Prize in Medicine for the molecular mechanisms of circadian rhythm | Hacker News Reader

2017 Nobel Prize in Medicine for the molecular mechanisms of circadian rhythm

nobelprize.org

178 pointssohkamyung41 comments

It's really exciting that this work is being recognized with a Nobel Prize. The company I'm working with (HealthRhythms - https://healthrhythms.com) is building products for understanding circadian rhythms and other behavioral patterns as they relate to mental health. There is an interesting body of research that suggests that understanding behavioral patterns and rhythms can help diagnose mental health conditions. And conversely, working with patients to correct and regularize their rhythms can be helpful in treatment. Here is a paper by one of our founders related to rhythm-based therapies in bipolar disorder:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202498/

As a company, we are using data from mobile phones (GPS, accelerometer, etc) to build rhythm profiles based on individuals' sleep, activity, movement, and phone use patterns. These profiles are then used to build personalized treatment programs to help people correct their rhythms. If you are interested in working on any of these, please do drop us a line (jobs@healthrhythms.com). We are looking for iOS developers and backend (Swift/Objective-C) developers (AWS and Python). I also posted in the Who's hiring thread so you can look there for more details

Aren't you basically foursquare but for health? Just taking a bunch of data, repackaging and reselling it to the health industry. I went to your site and I don't see anything besides "we take a bunch of data and apply machine learning" and other fluffy writing. It reads like snake oil.

"We take a bunch of random data and somehow do some ML stuff and something something mental health... here's some pictures of a old people!"

Maybe I'm too dumb or don't understand what you're doing but this was my first impression.

My thoughts exactly. The data isn't totally random but it's most likely very lacking in many ways. Yet another example of how perfectly correct math will most probably lead to wrong results due to false premise

For those interested in learning more about circadian rhythms, I highly recommend checking out the materials that UCSD's BioClock Studio has put out. As you might be noticing, there's a dearth of accessible circadian biology materials. The BioClock Studio has interested undergrads create movies and media addressing critical circadian biology concepts, experiments, and researchers.

https://ccb.ucsd.edu/the-bioclock-studio/about-bioclock-stud...

If you want a great book on the history of Drosophila research including circadian clocks and the genetics of memory, get Jonathan Weiner's "Time, Love, Memory"

All three Nobel Prize recipients appear often.

Seymour Benzer is an amazing scientist, and using of drosophila for neuroscience questions basically stated from his lab. And that book is a wonderful read

Can someone explain what is the feedback mechanism to self-correct the clock? This biological clock like any other clock will deviate from the true time after a while, maybe weeks or months; so what is the self-correcting mechanism in the biological clock?

It's been several years since I took my neurobiology class in undergrad. There has been a lot of research in this area. You're right that the clock does deviate (I checked Wikipedia and it looks like in the absence of light humans' circadian rhythm cycles on just over 24hr). Exposure to light helps tweak the cycle.

https://en.wikipedia.org/wiki/Suprachiasmatic_nucleus

The SCN receives input from specialized photosensitive ganglion cells in the retina via the retinohypothalamic tract. Neurons in the ventrolateral SCN (vlSCN) have the ability for light-induced gene expression. Melanopsin-containing ganglion cells in the retina have a direct connection to the ventrolateral SCN via the retinohypothalamic tract. When the retina receives light, the vlSCN relays this information throughout the SCN allowing entrainment, synchronization, of the person's or animal's daily rhythms to the 24-hour cycle in nature.

And importantly, the photosensitive ganglion cells are most sensitive to blue wavelengths of light, which is why a lot of people recommend avoiding blue light at night.

Off-hand I do not have a good reference (maybe this? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078443/ ) but I've heard quite often that both light and food have an impact on our body clocks, and that the systems operate more or less independently. Perhaps someone out there who knows more can clarify.

It is entrained to rhythmic external cues, synchronised oscillators.

Ooh, I read about this in a neuroscience text book I've been nibbling at for a few months now. Really cool to see a Nobel prize for something I've just recently studied.

Isn't it cool how gene systems are hybrid digital/analog computers?

Which book?

Would you recommend it?

Principles of Neural Science 5th ed. By Kandel et al. It was recommended to me here on HN.

The thing is a serious tome. When I want to work through a chapter I have to make time every day for a week and keep notes. In any case it has a lot of technical detail which is specifically what I was looking for.

Hmm, 1981. Neuroscience has evolved considerably over the last 35 years. Is it still worth reading it now, over more modern texts?

Most recent edition was published in 2012. It's extensively updated between editions, so very much worth reading if you are seriously interested in neuroscience.

Thank you, I will give it a look.

If you have some prior knowledge of neuroscience you can give it a cursory read in a day or so.

You probably do yourself a greater favor reading it and overwriting fragments of knowledge later, than you would by not reading the whole textbook at all.

Very cool indeed! I'm lately reading a lot about temporal system design and got fascinated with clocks and our notion of time. Interesting how, if I understand it correctly from this article, our own "clock speed" is the rate of degradation of the PEP protein. Also interesting that people who spent a long time in isolation (eg. in cave experiments) had their internal clock drift considerably from our normal 24 hour cycle, which suggests that the environment does affect it.

>Isn't it cool how gene systems are hybrid digital/analog >computers?

I think it's more correct to say that computation is an emergent property of living systems, but is by no means the only thing they are capable of.

This is a perspective I wish was echoed in University halls.

I would not call gene systems computers. They may be programmable, but they do not generally do computation (that's not to say you can't force a gene systems to do very crude computation).

Interesting work, but the explanation seems a little at odds with research in artic mammals:

https://www.wired.com/2010/03/arctic-reindeer-circadian-cloc...

Or at least, it appears there's even more complexity around this than the mechanism sketched out in the summary.

As somebody who is currently 9 timezones away from home and just barely beginning to be normal (going back home tomorrow, of course) I was kind of hoping that they would have some sort of procedure, drug, diet or otherwise advice on how to avoid or compensate for jet lag. Im glad they know about its mechanisms, but I sure would like some applied science in this topic.

Before leaving, figure out what time breakfast is in the timezone you're traveling to. Then, 12 hours before that time, start fasting. When you arrive, have breakfast at a normal (for your new time zone) time. Your circadian rhythm will reset almost immediately.

Thanks, I will try that.

You could also take some viagra. https://www.newscientist.com/article/dn11895-viagra-reduces-...

This is something international flights are partly to blame for.

If I take an 8 hour flight to Europe, overnight, I'll be served dinner and breakfast, but much closer together than 8 hours. I'll sleep maybe, and by the time I get there, my body is truly confused.

Last time I flew, I stayed up the entire flight and didn't sleep until midnight, destination time. I was the most adjusted person in our group. Next time I'll try your fasting recommendation.

You can have your physician prescribe you a course of melatonin. https://www.ncbi.nlm.nih.gov/pubmed/12076414

Medicine? So I just learned something right now. There is no Nobel prize for biology.

The HN title is slightly off; the full name of the prize is "Nobel Prize in Physiology or Medicine".

so, can it be that injecting PER protein would cause a person to feel great, full of energy like in the morning ... and may be actually capable to run 100m in 8sec or to drive that truck (or Navy destroyer) non-stop for additional 20 hours in a row :)

I understand the Nobel committee's desire to see results validated many times over before making an award, in order to avoid embarrassment should the findings be overturned as has happened in the past. I also acknowledge that the research cited here is very significant and important...but...the research being awarded is over 30 years old! To say there's not been any more noteworthy and validated discoveries in Medicine since the mid '80s, well, I just don't buy it.

Just for starters, the fact that Venter still does not have a Nobel is a crime and, in my mind at least, an irrefutable indictment that, in Academia, politics and "playing by the rules" is valued far more than actual results.

> but...the research being awarded is over 30 years old!

This is not irregular for the Nobel and Nobel-like awards.

> To say there's not been any more noteworthy and validated discoveries in Medicine since the mid '80s, well, I just don't buy it.

Who said otherwise?

> in Academia, politics and "playing by the rules" is valued far more than actual results.

The Nobel is an award whose supply is -- by design and definition -- massively and artificially constrained. Politics is just what happens when there are fewer resources than people who by all accounts deserve the resource. So Of course such awards are political. Your observation is just a tautology.

Also, you can replace "in Academia" with "in life" and the statement will be just as true.

> Just for starters, the fact that Venter still does not have a Nobel is a crime

Okay, and what about all of the other names that also could have come after "Just for starters"? Not everyone who deserves a Nobel will get one. That's life.

I'm not sure that Venter should get a Nobel. He has played a big role in science over the past 2 decades, but I'm not sure that any of his accomplishments are Nobel-worthy. I certainly don't think he will get one for his work on the genome project. The genome project was such a large effort that involed so many people that I can't imagine selecting a few figureheads to recognize with a Nobel.

Venter led the team to sequence the first genome of a free-living organism. Before Venter left NIH to start Celera, the Human Genome Project was entirely focused on making long, pre-aligned reads. It wasn't until Celera started embarrassing the NIH effort that shotgun sequencing was taken up in earnest. Later, his idea of then taking shotgun sequencing and applying it to whatever DNA you could find floating in the Sargasso Sea or any random teaspoon of dirt literally opened a whole new world of evolutionary biology. Finally, his more recent work on creating a fully synthetic organism is continuing to push forward the bleeding edge of biotechnology by laying a foundation all of humanity is sure to build on for decades to come.

But that one time he told investors that he'd pay for his research by patenting gene sequences (something he never actually, AFAIK, did do), and all his accomplishments may as well be nothing in the eyes of some.

I'm very aware of what Venter has accomplished, but I don't think sequencing Haemophilus influenza is more impactful than sequencing PhiX or phage and don't think it deserves a Nobel. I don't think a Nobel should be given out for the sequencing of the human genome. It was a large, systematic effort that didn't require much clever experimentation. I also don't think his post-Celera work deserves a Nobel. These are just my opinions. He's obviously a huge figure in modern science and I love hearing about him and getting to watch him speak.

> It wasn't until Celera started embarrassing the NIH effort that shotgun sequencing was taken up in earnest.

Sure.

But I disagree with the overall premise and think you're over-simplifying in the extreme. What really made the Human Genome Project possible was the Moore-like curve in sequencing throughput that occurred throughout the lifetime of the Human Genome Project. There were many contributing factors that kept the curve going (including the other Moore curve!)

Also, Sangar never got a Nobel in Medicine (just in Chemistry). So even if shotgun sequencing is the idea that deserves the Nobel for Human Genome Project -- which again, isn't exactly an incontestable assertion -- then it's Sangar, not Venter, who was robbed. Awarding Venter with a scientific award for his political work pushing Sangar's science would be an odd choice, not to mention at odds with your apparent overall feelings about the role of politics in Nobel awards.

Which... maybe they both deserve a Nobel for their contributions to the Genome Project. Probably so, in my opinion. It's almost like the supply of Nobels is artificially constrained and not everyone who deserves one can get one...

> Later, his idea of then taking shotgun sequencing and applying it to whatever DNA you could find floating in the Sargasso Sea or any random teaspoon of dirt literally opened a whole new world of evolutionary biology.

Lots of people use shotgun sequencing for all sorts of high-profile and important stuff that is literally opening a whole new world of all sorts of important fields.

And there's a lot of stuff going on outside of genetic sequencing that also deserves Nobels.

> Finally, his more recent work on creating a fully synthetic organism is continuing to push forward the bleeding edge of biotechnology by laying a foundation all of humanity is sure to build on for decades to come.

So maybe a Nobel will be awarded in the decades to come. Nobels are given for impact, not promise, and impact takes decades to accrue even for the most impactful work.

I would never say someone like Venter "doesn't deserve a Nobel". But getting all bent out of shape that he doesn't have one is kinda weird, especially since he's not exactly starved of other sources of recognition -- both inside and outside Academia -- for his contributions. Lots of people who played outsized roles in the Human Genome Project exist in relative obscurity relative to Venter. Which isn't to say he doesn't deserve his recognition, but I just don't understand the particular drum you're beating here.

>Later, his idea of then taking shotgun sequencing and applying it to whatever DNA you could find floating in the Sargasso Sea or any random teaspoon of dirt literally opened a whole new world of evolutionary biology.

This field is called metagenomics and Venter did not come up with the idea nor was the first to publish in it. There was a 2002 paper of shotgun environmental DNA sequencing on viral communities, and the Tyson + Banfield 2004 paper came out in March while his came out in April. Craig gave metagenomics some needed publicity but I don't think anyone would say he advanced the field or contributed much to how metagenomics is done today.

Venter is a celebrity, not a basic scientist.

Yes, he contributed greatly to the HGP. Yes he spurred on a lagging public project. Yes, he founded multiple scientific institutes.

But the HGP would have been completed without him. He offered no new insight or idea that changed the fundamental understanding of biology. He is famous, and deserves that fame, but does his ideas and research deserve a prize? We'll see, but certainly not yet.

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