Episode Transcript
[00:00:00] Speaker A: The jerky motions of the ship give way to a steadier, more stately motion.
Okay, your tour guide says, go ahead and open your eyes.
When you do. There, before you, on the other side of the submarine's main viewing window, is an enormous cell. Or at least it appears enormous, since you and the submarine have been shrunk down to a tiny fraction of the cell's size.
ID the Future, a podcast about evolution
[00:00:31] Speaker B: and int in design.
Imagine for a moment with me that you've been invited to a futuristic discovery center, a lavishly funded facility that has pioneered the ability to shrink people and objects many orders of magnitude. Now imagine you could climb aboard an incredible shrinking submarine and travel into the heart of a living cell.
This would be a tour like no other. You'd get a glimpse of DNA, molecular machines, cellular architecture. But you'd also bear witness to the workings of a hidden world of information and epigenetic controls operating beyond the physical structures of Life.
Welcome to ID the Future. I'm your host, Andrew McDermott. For decades we focused on DNA as life's master blueprint. But modern discoveries have revealed additional layers of information that help direct, regulate and coordinate cellular activity.
These systems, collectively known as the epigenome, have opened an exciting new frontier in biology.
In their new book, Epigenetics and the Architect, historian of science Dr. Tom Woodward and his co author, Dr. James Gills, explore this frontier in depth.
Now. Today, Dr. Woodward reads to you from the new book and rather than beginning with definitions and diagrams, he invites us on an imaginative journey inspired by sci fi movie classics like Fantastic Voyage, Inner Space or Honey I Shrunk the Kids. So buckle up, close your eyes and prepare to shrink to microscopic size. As Dr. Woodward guides us through the bustling inner world of the living cell to give you a chance to grasp just how information rich cellular life really is and why it can't be so easily explained away when by Darwinian evolutionary processes.
Here's Dr. Tom Woodward now reading from Epigenetics and the Architect.
[00:02:28] Speaker A: I'm Tom Woodward and I'd like to read you an excerpt from the new book Epigenetics and the Architect, which was just published and it was authored by myself and Dr. James P. Gills.
This is from chapter three, A Voyage through the Cell.
20,000 bots under the sea.
Imagine you have been invited to a futuristic discovery center, a lavishly funded facility that has pioneered the ability to shrink people and objects many orders of magnitude. A wild fiction to be sure.
Even if such miniaturization were possible, any number of fine tuned parameters of the laws and and constants of physics and chemistry that make organic life possible would be thrown into havoc by the miniaturization.
We would arrive on the other side decidedly dead.
But that never stopped Ant man or the Magic school Bus or the Solinsky family and honey, I shrunk. The Kids or the Crew of Inner Space.
Or, for those readers with even longer memories, the Incredible Shrinking man or the Crew of Fantastic Voyage.
So let's climb into the Incredible Shrinking submarine with our tour guide and begin the journey.
The strange vessel is equipped with panoramic windows in every direction.
As you buckle in, everyone is encouraged to close their eyes.
A launch countdown sounds over the intercom.
You feel a bit of vertigo, as if a recklessly fast elevator were speeding downward from the top level of a skyscraper.
There's a shrill metallic ringing, and then both the sound and all sense of motion stops.
A moment later you're jerked back into motion, but now the motion feels like that of a ship in roiling waters.
Your piloting tour guide, seated with you and the other members of the tour in the spacious cockpit, raises a hand to signal that all is well.
They're moving us into position, he explains.
Just a few billionths of an inch from the water engulfed surface of a living cell, the jerky motions of the ship give way to a steadier, more stately motion.
Okay, your tour guide says. Go ahead and open your eyes when you do. There, before you, on the other side of the submarine's main viewing window, is an enormous cell. Or at least it appears enormous, since you and the submarine have been shrunk down to a tiny fraction of the cell's size.
The vessel approaches the outer surface of the cell and slips into one of the many gates in the cell wall.
Now all around you are the bobbing heads and the trailing fronds that form the cell wall's double layer lipid membrane.
After squeezing through the dark curtain like structure, your vessel passes into the cell interior, marked by a lattice like maze of beams and girders.
It looks as if some gargantuan and enormously intricate skyscraper were under construction beneath the sea, with all the interior pillars, trusses and girders laid bare in a vast underwater cavern.
Your guide gestures with a sweep of the hand.
What you see all around you is the internal structural skeleton of the cell. Most of you are familiar with DNA, with genetic information will encounter plenty of that.
But some of the cell's most important epigenetic information is embedded here in the precise way that these structural girders are positioned and attached to the cell membrane.
This informational pattern is especially important in a newly fertilized cell, the zygote.
Even when it is still just a single undivided cell, the zygote has far more information in its 3D structure than we imagined.
Far more than just what is rooted in its DNA.
After descending through a maze of tubular branches, braces and beams, you spy ahead the nucleus, the spherical storehouse of the cell's DNA.
At the tiny scale you and the sub have been shrunk to, it looms as a huge, shimmering globe, an underwater city whose surface teems with the traffic of complex molecules shuttling to and from its surface.
As the sub draws closer, you see that the molecular blobs pass in and out of the nucleus via hundreds of large circular pores in the wall of the nucleus.
Each portal has tiny hairs protruding around the entrance. The submarine approaches one of these portals and slips through.
Arrayed before you is a vast and crowded underwater arena.
Hundreds of isles penetrate the maze of stacked loops and clumps of DNA in every direction.
Your tour guide pilots the sub into one of these narrow aisles and aims the sub directional search light on a wound up mass of DNA.
You know those spools and sewing boxes with the thread around them? He says.
Here the DNA is the thread and the histone complex is the spool.
Only, as you can see, it's a lot less tidy than a sewing box spool.
Don't sell it short, though. It's an engineering wonder, enabling DNA to be compacted to an extraordinary degree.
Each histone protein, reminiscent of a tiny clump of pasta, is a string of 100 or so Amino acids precisely folded into an irregular Z shape.
Once folded, eight of these histone proteins combine like a three dimensional jigsaw puzzle to form the ideally shaped spool called the histone core.
In human cells, millions of histone cores are produced as the cells divide and stand ready for the new DNA to be wound around them.
Your pilot tour guide points the searchlight at something odd sticking out of a spool on one side, it looks vaguely like a thin branch or a tail.
As the sub draws closer, the pilot illuminates three other tails. Like the first one, each histone core is equipped with eight tails. You can spot four of them on the side facing us.
He narrows the spotlight beam and it trains it on the strange Y shaped tag attached to one of the tails that seems to be bulging out and pulling away from the histone bundle.
Note what is happening here, he says.
The little molecular Y tag is causing the whole tail to be steadily pulled away from the layers of DNA on the spool.
This is a key marker in the epigenome system.
The tag is an acetyl molecule attached to a precise spot on the projecting tail of the histone spool. With the help of a special protein machine, this particular tag functions as an unlocking device.
When the acetyl tags are placed on the tails, those tails swing away from the spool, and this makes it much easier for the file of DNA that is wound onto that histone to be pulled off and ready.
On the other hand, if the acetyl tags are removed by a different protein machine, the slender histone tails snug up closer to the DNA wrapped around the spool, allowing the tail to act like a clamp, securing the DNA tightly onto the spools and making it harder to be read.
It's like a locking and unlocking system on a filing cabinet.
These acetyl tagged histone spools are all over this DNA warehouse. If we tried to count them all, we'd be here a long time.
The information required to manage the precise placement of acetal tags, something like a dynamic 3D map, is stored beyond DNA.
It's epigenetic.
Outside the submarine window, a protein machine suddenly swoops down and removes an acetyl tag from the spool.
That's a histone deacetylate enzyme, or hdac, engineered to grab and remove tags. The pilot says its complementary protein machine, histone acetylase enzyme HAC for short, attaches the acetyl tags.
If all that is not complicated enough, there are four other chemical tags also found on those tails.
You sense a hum and also a low vibration.
The intensity builds steadily.
And then there's a voice over the intercom.
It's mission control. Incoming. Take evasive maneuvers.
Roger that, says your guide, and deftly maneuvers the submarine away from the DNA spool.
The ominous vibration persists.
But then a broad smile breaks across your guide's face as he looks toward the far end of the narrow DNA corner order.
We're in luck, he says.
We happen to be in a section of chromosome 17 where a key stretch of DNA is being opened and read.
The vibration you're feeling is the rumble of the big protein machines lumbering along the stacks of DNA just ahead.
They're unlocking and prying open very specific sections of the DNA spool clusters.
We call these clusters nucleosomes.
The goal of the machine is to gain access to the target cluster of genes.
The pilot seems to have forgotten all about the command to take evasive maneuvers. Instead, he aims the sub directly into the action.
A frenzy of strange underwater robots carrying scurrying around the tiny interconnected islands of DNA.
One slice of the action stands out as the genetic corridor opens wider.
Several DNA manager bots swarm down on the DNA, grabbing, twisting and rapidly unwinding sections of it from their spooled up position on the histones.
Soon they have the DNA molecule unfurled.
At first, the double helix up close looks like fuzzy yarn.
But as the sub draws closer, the DNA's elegant spiral ladder geometry comes into focus.
Its unique form looks like what it is depicted as in textbooks.
Except the rungs are knobby and thick with almost no space between them.
The tour guide pilots the sub down along the spine of the DNA and as they pass by, you get a close up of the smooth surface of the DNA letter pairs the rungs in the twisted ladder.
Your guide aims the spotlight at one of the rungs.
Notice here and there the smoothness of the rung pattern is marred by something sprouting from the rung.
A tiny antenna like appendage resembling a baby sprout of broccoli.
No, it's not an unfortunate growth.
The molecule is a chemical marker called a methyl tag.
In its free state as methane, it has five atoms, one carbon and four hydrogen. But the methyl group has one less hydrogen atomic 3 instead of 4.
So think of the methyl tag as a stripped down methane molecule, A minor variation on the gas molecule burned by the trillions in any stove fired by natural gas reachers.
Researchers discovered this tag in 1948 and they learned that it gets attached to only to the C letters in DNA's four character Alphabet, and only to some of them.
Methyl tagging is one of the core features of the epigenome.
Tens of millions of DNA rungs are tagged this way.
And it was discovered that this tagging pattern is indispensable to cellular function.
The specific letters getting tagged are chosen for functional reasons.
Some molecular biologists describe the tagged Cs as the fifth letter of DNA.
On this view, there is a T, C, G and methylated C.
That last letter is crucial.
Typically it acts as an off switch for for the stretch of DNA where it's attached.
If all these stretches were on all the time, we could expect a nasty multimolecule pileup.
Some scientists estimate that as many as 200 million methyl tags have been placed on precise locations on the DNA in a single nucleus.
The tour guide checks the subs instrument panel and then resumes his commentary.
When a cell divides, the entire genome is opened up to be duplicated.
All the billions of rungs of DNA are split open and replicated.
So do all these methyl tags get copied into the bargain?
No one answers.
This answer goes unanswered, beyond a reticent nod of the head from a fellow passenger. Exactly, your guide replies, seizing on the weak gesture of ascent. The methyl tags are also copied over to the same corresponding rung in the new cell's DNA.
The how is interesting. The job falls to a special protein machine, a methyltransferase.
But there's a catch. The pattern of methyl tagging varies from cell to cell, and while this methylation map is generally passed on unchanged from mother cell to daughter cell, there are untold thousands of exceptions, especially when an embryo is developing.
The differences are essential, and the source of the differences isn't limited to DNA.
He checks the instrument panel again and then straightens in his chair.
Oxygen supply is getting a bit low. Time to make tracks.
If the lazy tune he begins whistling is any indication, he's expecting an uneventful return journey. But after your vessel passes through the lipid bilayer membrane, it is only past the cell wall for a moment before a second cell, an angry looking bacterium, bears down on your ship.
That's the end of our reading from chapter three of Epigenetics and the Architect.
I'm Tom Woodward. Thank you for joining us.
[00:19:52] Speaker B: That was Dr. Tom Woodward reading a memorable passage from his new book Epigenetics and the Architect, co authored with Dr. James Gills. That was from chapter three of the book titled A Voyage through the Cell. The book is available now through Discovery Institute Press. You can get your own copy, or a copy for a friend at Discovery Press.
That's Discovery Press.
And don't miss our two part conversation with Dr. Woodward unpacking some of the key insights of the book.
Find that two part conversation in in separate episodes of the podcast for ID the future. I'm Andrew McDermott. Thanks for tuning in.
