Regulated cascades pop up all the time in biology—particularly in complex organisms. Whether coagulation, development or differentiation of specific cell types, they all follow the same general pattern. To keep things simple, I’m generalizing this whole idea into the task of making a birthday cake:
Creationists—particularly those under the guise of intelligent design—love these. How could something as complex as the coagulation cascade simply appear, intact and whole, due to random chance? There are no intermediate steps where small refinements can be selected for! It’s all or nothing, baby! You know what that means….
Proof of GOD! Praise Jesus!
Really? Some new work, in the field of skeletal muscle differentiation, points to another way beyond the divine to generate a cascade.
If we’re going to figure out a way something could happen by evolution, it’s important to show each step has something can can be refined by selection for the most successful versions.
Let’s say the master regulator here (“Let’s make a birthday cake”) starts off as quite promiscuous, willing to turn on a whole set of tasks all at the same time—some things you’d want in cake, some things you wouldn’t.
The cake is going to be pretty bad. Things that do not belong in cake are going to end up in the finished product. Likewise, the order is all off. It would serve as a cake-like substance, but there’s much room for incremental improvement. For example, “apply ketchup” would be strongly selected against.
We also have something wrong here. The sub-regulators (“place candle” and others) also must be turning on a whole bunch of other smaller tasks. Why couldn’t they be turning each other on as well?
We get a cake again, and a little better better one at that. Now, over time these in-order connections between the sub-regulators will get selected for until they’re nearly as strong as the master regulator. (The out of order connections between the sub-tasks would be selected against; they’re in dashed green to indicate this.) If both the master regulator and the previous sub-regulator must be turned on in order to activate the next step, the result would be a pretty damn good cake. Therefore, natural selection will pick out those cascades with that trait.
The better ordered these steps, the better the cake turns out. So, the strength of the connections between steps, relative to that of the master regulator, will increase.
Eventually, the master regulator will only be able to turn on the first step. The result? A neat cascade:
This isn’t just speculation on my part. Scientists studying the differentiation of skeletal muscle cells have found direct evidence for this sort of evolutionary process. Pretty cool.
Yes, pretty cool. Thanks for sharing.
Jonathan,
What species are the embryos in your lab?
Based on these diagrams, I would guess chicken.
@2: None. In fact, in my now decade plus in laboratories, I’ve never worked with an embryo of any species. At all. Nor does anyone in my lab.
Your very question tells me you’ve never read a single thing I’ve written about pluripotent stem cells.
I’m writing a detailed post on the ethics of pluripotent stem cell research. Please refrain from any more off-topic comments until it goes live. Else, you run the risk of your comments being deleted and being banned permanently from slog. And I want your comments on that post.
But, for now, chew on this: The disease the lab I work in studies causes the death of over 2000 human beings each day. And our work was delayed and hampered significantly by the federal funding ban.
Remember: Stay on topic! Don’t get banned!
#2, Devil’s food.
This is cool shit. I kind of got the idea studying complement cascades in immunology, but this is a good layman’s explanation. Thanks, Golob.
@2 – This isn’t from his lab. What’s your point?
That negligent parent cake looks like most of my cakes. They still taste good though, probably because I withheld the ketchup.
But they aren’t innocent baybeez!!!
Sure.
BAN posters who ask uncomfortable questions!!
Very Marxist Nazi.
Chew on this-
Embryos are living humans.
How many humans should we experiment on to find cures?
Should we ask them before we experiment on them?
If they are totally powerless and helpless does that make it OK?
Because they are small and don’t cry out does that make it OK?
Why do the brilliant scientist on the verge of curing all disease refuse to address the issue of the humanity of Embryos?
I guess even Science has it’s limits.
BAN ME IF YOU WANT.
COWARD
Perhaps years experimenting on the helpless leaves “scientists” unable to cope with awkward questions.
Arguing with America-hating and Science-hating “creationists” is pretty much a waste of time.
Self prorogation is really the most basic of life’s properties.
Really, life in general could be said to be a sort of cascade, regulated by the need for sustenance and the processes of natural selection.
It seems a simple thing to me, to imagine a substance that just happens to develop the properties needed for self replication to become a cascade and to later be shaped into the forms we now call life.
One interesting area of study that actually takes that idea and reverses it involves prions. These organic molecules, originating from mutation, are not alive on their own but replicate themselves by altering other body proteins into their own form. Ironically, they do so until they have exhausted their supply of food and their host organism dies, as a result. This is the cause of mad cow disease and similar afflictions.
It’s also thought that many viruses have arisen, throughout history, from the very DNA/RNA they later infect.
Anyone that thinks we’re created in the image of a prefect, omnipotent deity has never had a hernia.
@8: It’s not that the questions are uncomfortable. They are in the wrong context.
You’d be thrown out of a movie theater if you insisted on screeching about HUMAN EEEEEMMMBRRRYYYOOOOS at the top of your lungs.
Most of us figure this sort of basic social contract stuff in elementary school. Were you home schooled or something?
To recap:
1. I offer, generously I think, to create a space and context appropriate for the topic you so desperately want to discuss.
2. I politely ask that you contribute your thoughts and ideas there.
3. I remind you that this community’s standard is to not repetitively comment about off-topics on every post.
4. I warn you of the concequences to which everyone who comments here are subject.
The response? You call me names (“Nazi… COWARD….”)
Somehow, despite your demonstrated lack of reading comprehension and social skills, I’m really not that frightened about anything you’ll write or say anywhere having a material impact on other people.
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Or hemmoroids
He’s using wheat embryos to bake cake.
marxist nazis self-destruct, right? They can’t handle themselves?
This is a good representation of the complex way complex things evolve. Thanks, golob.
@DougSF: Or a kidney stone. Or any sort of shoulder-joint problem. Or given birth to a child…
The talk I went to that presented this idea fascinated me. Evolving cascades is a non-trivial problem central to most complex life. I loved seeing the work it took to unravel it.
@Arsenic7: Oh, absolutely. One of my other favorite areas of evolutionary biology is the interaction between parasites and hosts. Diseases appear to be one of the key accelerators of natural selection–shifting the genetics of entire populations with startling speed. See, smallpox in Europe for an example.
As always, another wonderful insightful post. Thanks for always being our helpful little scientist. 🙂
#15 – You’re right, but I didn’t just mean the pain or something that wear out. Our propensity for hernias seems to be special sort of fail in our “design”, with no real reason for correcting itself over the next 1,000 generations, should we make it so far. I mean, it doesn’t seem like too much to ask for our guts to stay in place, and yet…
Our bodies are pretty fuckin’ impressive machines, but it’s definately one of the reminders we turned out far from perfect.
It would make perfect sense and that’s how they do things on more advanced blogs like Blogtown, PDX, but you can’t ban people right now… you would have to ban everyone who uses Comcast or everyone who works at Microsoft. That’s why the same trolls have been posting racial slurs on all of Charles’ posts for months, for example. I sympathize with you 100% though. Also, I liked your post.
Sorry, but embryos aren’t living humans. Your entire argument fails right there. The first point isn’t open to discussion. Please move on.
Also, your post makes me think a bit about why in the world some people find the whole blind watchmaker theory so comforting.
Ever just watched some of the creation science videos of Christiantube?
The one about bananas is just a mind boggling display of false logic.
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They are alive.
They are Homo Sapiens.
questions?
(be careful, you’ll get banned)
I would prefer it if some cake variants would conserve the ketchup gene, and use mRNA to turn it back on sometimes.
Or maybe have the siRNA turn off the apotosis gene that kills Republicans only some of the time.
A lot of what we think of as noise in the gene sequence actually isn’t. Sure, some is just viral encoding or dead adaptations, but some is put there for adaptive purposes, and it doesn’t make sense to turn on just one segment when you need a whole group turned on all at once to make it function.
Jonathan, you make precisely the point. Science is working to make life better. Religion is working to make life hell. It’s really too bad we should even have to waste any time trying to make some understand. But there is also the chance that in doing so there are those who will see the light. Thanks for your work.
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Please excuse my intemperate exuberance.
But it (@2) is a simple question, that has been left hanging from two previous posts.
And it is an issue that is ducked and dodged.
And threatening to ban over it seems heavy handed, and cowardly.
I look forward to the post you described.
And appreciate your posts and comments on slog.
It doesn’t matter. You could have unquestionable proof that there is no god and the uber-religious would STILL believe in god. They will believe in god no matter what. They don’t even really want proof either way that god does or does not exist, believing in god makes them feel happy, so they’ll keep doing it regardless.
And there will always be plenty of nuts within their ranks who insist and demand that WE all believe in their god too… you know, so we can be as happy as them or some shit like that.
That being said, I really love how you demonstrated this with the metaphor of the cake, Jonathan.
@2: He uses human and mouse embryonic stem cells. Specifically, undifferentiated H7 (WiCell) human embryonic stem cells and undifferentiated R1 mouse embryonic stem cells
We get all our stem cells at K-mart.
My individual skin cells are alive, and their nuclei are filled with human DNA… my skin cells are each “homo sapiens.” They’ll even grow “on their own” if carefully cultured under very precise condictions… That doesn’t mean that my skin cells have rights.
Every time a doctor performs a biopsy, they’re removing and “killing” living tissue that is every bit as capable of functioning and growing independently as an embryo. The only difference ex vivo is that, for the most part, cultured adult cells can only stay the same type of cell, but embryonic cells can be cultured into different types of cells, making them hugely more useful for research. No one reasonably believes that those biopsied adult cells have rights.
I won’t claim that I know where the legal boundary should be between “tissue” and “person.” I thought of my daughter as a person long before she could have survived on her own outside my uterus. However, it’s dangerous to define a “person” as any living human tissue. Then do my biopsied skin cells have rights? Does a non-functional but “living” parasitic conjoined twin have rights? Do we want to define it as “murder” if a woman undergoing IVF ends up with 8 implanted embryos and terminates some of them to avoid becoming octomom? Do we want a woman who miscarries in her second month of pregnancy to have to fill out death certificates?
Actually this does provide me with a sort of general science question to ask Jon.
Are the basic reasons for cascades involving organic molecules and tissue different than the self prorogation activity seen in inorganic compounds, like what happens in crystal seeding? Is there any relationship to be made?
Very good article, Jonathan. I will use this cake metaphor to teach my biology students about evolution.
Can I just add that I freaking love science metaphors, both as someone who loves to learn about science and someone who loves to talk to others about it.
A good one can mean the difference between complete confusion and that light bulb moment.
kebabs: If you send me an e-mail at dearscience@thestranger.com, I’ll give you powerpoint slides with these graphics.
Arsenic7: This gets out of the depth of my post, but only somewhat. Both are somewhat autocatyltic processes. But, living systems do this in a slightly deeper way.
It has to do with the step before my starting figure: All of the boxes in my figures come from one parental protein that got cloned, and then started to diverge through mutation over time.
I know this is cryptic. I’ll try to write something on this in the future….
The question of the species of individual cells or a mass of undifferentiated cells is completely specious and irrelevant. An egg and a chicken may be of the same species. Is an egg the same thing as a chicken? Is a caterpillar the same thing as a butterfly?
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A (human) embryo is “a” Homo Sapiens.
Your skin, nail clippings, biopsy specimens etc are pieces of a Homo Sapiens.
The hypothetical situations and questions you pose get ahead of the story and range beyond ‘science’ into ethics and law.
First, Science can (and must) inform when life begins. Society then takes that information and develops laws etc to reflect it.
All I wanted was a pleasant and thoughtful discussion about evolution.
Your poor manners disgust me. I’m writing your precious ethics post right now. It’ll go up on slog. You can make your case, over and over again, there.
After that, I suggest you start your own blog. http://golobiswrong.blogspot.com/ seems to be available. You can write, for free, hundreds of posts a day about HUMAN and ‘A’.
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There’s no rush, Jonathan.
Perhaps you need a nap.
How many minds have you won over with your general assholery? Does it bother you to be so impotent?
Awesome! Science is nifty indeed.
See, this is my problem with cakes–I keep icing the candles before baking the cake.
Jon, don’t let these guys get to you, bud.
Think of it as an opportunity to study the spontaneous genesis of trolls from irrelevant posts.
I loved the post! Bringing it down to the simple pictogram helps explain these things to people who really are interested.
Of course then there are the damn people who say: “oh yeah? well Darwin couldn’t explain eyeballs! haha! that means everything you say is wrong”
(real quote from a baha`i faither claiming to want to understand my point of view)
Discussion is not what they really want. Don’t feed the trolls.
Jonathan,
can you explain slog troll genes keep strongly selecting for ‘ignorance’ in the presence of science instead of ‘common sense’?
Enjoy here or here.
Thanks for the kind words, Arsenic7, lemonrose and Y.F. I’m going for a drink.
An egg is not a chicken. Yet.
A grub is not a beetle. Yet.
A maggot is not a fly. Yet.
A caterpillar is not a butterfly. Yet.
An embryo is not a person. Yet.
This is such an awesome analogy! I <3 biochemistry!
I think your cascades are excellent. I was a biology major for awhile and would have probably stuck with it if some of the lectures had been this fun.
Idea: it’d be cool to discuss the evolution of the vertebrate clotting cascade. That’s a fun one, because it debunks the wrong-headed idea that mutations can’t produce new information.