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This is KZSU Stanford.

Welcome to entitled opinions.

My name is Robert Harrison.

And we're coming to you live from the Stanford campus.

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Many people think that the human mind, its capacity for speech, analysis and abstract thought,

is evolution's greatest achievement to date.

But consider the following.

We have created computers that can defeat the most intelligent chess players in the world.

Yet when it comes to making a machine that can move through a room without bumping into objects,

we're at a complete loss.

Our mental powers are relatively easy to reproduce artificially,

while our sensory motors, our perception, our bodily coordination,

present a hopeless challenge to the science of robotics.

Why?

Because on the vast scale of geological time,

our intelligence is a very recent phenomenon,

the most insubstantial part of our natures,

while evolution has had over 3 billion years to perfect our bodies.

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That's right, my friends, an ordinary animal's ordinary ability to move through a room adeptly.

That's the miracle.

The body is for the most part a silent marvel.

If we had any idea about all that goes on in our organisms,

as we put on our shoes, carry on our daily business,

pursue our petty rivalries, gorge ourselves on foul food stuffs,

transfix ourselves to the computer screen,

obsess over our mating rituals.

If we had any idea how our bodies at any given moment

are pollulating with interstellar signals and transactions,

even as we lie still, we could hardly get through the day.

The chemical process, by which a tear wells up and falls from our eyes,

practically defies comprehension.

Yet this doesn't stop us from tearing up at the end of the Thelma and Louise,

which, by the way, just for the record I consider an excellent movie.

My point is that our bodies are infinitely more intelligent

than our conscious minds, which are really quite crude by comparison.

This goes for the bodies of all other animals,

as well as the organic fabric of plants and even bacteria.

My point is also this, that we take it all for granted

and fail to appreciate the wonder of it.

It's tragic but may be also inevitable,

that as long as we are alive, we tend to devalue

the most extraordinary gift the cosmos has to offer,

namely embodied life,

sentience, perception,

eyesight,

instead we hank her after a new car.

Back in January, we did a show with Stanford physicist Andre Linde

about the inflationary universe.

We were reminded then about the mind-boggling dimensions of the house we live in.

Over 200 billion stars in our own provincial galaxy,

which is one among billions of other known galaxies,

in a universe which, if Linde is right,

is one of many, if not countless, universes out there.

The cosmos is the wonder of wonders, and yet,

and yet.

It is not more wondrous than a living cell.

In fact, if the living cell were not ultimately a part of the universe,

it would be more wondrous than the universe itself.

Those of you who follow this program with any regularity know that I have my problems with modern technology,

especially biotechnology.

Yet I believe that technology and science are distinct phenomena driven by very different motivations.

For all my suspicion towards technology,

my enthusiasm for science knows no bounds,

not because I have a passion for explanation,

but because science provides us with endless evidence for the existence of miracles.

Not in the supernatural sense, but in the sense of extreme improbabilities.

The more we learn about the biotic, its levels of organization,

its integrated complexity, its reproduction patterns,

the more unlikely and improbable it becomes.

Science does not demystify and disenchant the world as many believe.

It in fact puts in sharp relief the ultimate mystery of things,

be it the cosmos, the biosphere, or the living cell,

to say nothing of ourselves.

Philosophers have long held that the greatest mystery of all is,

why is there something rather than nothing.

I agree with that by and large,

but I don't want to discount the wonder of the something in its own right,

independently of the fact that it exists at all.

What I mean is that this something is in itself quite amazing.

The proof being that the more we know about it,

the more we realize how little we really know about it.

In other words, knowledge adds to rather than subtracts from the reservoir of the unknown.

That's why I prefer science to God.

By standing in as the primal cause of the something that is,

God dispels the mystery.

Science by contrast, in its empirical investigation of the natural world,

augments the mystery by revealing its inexhaustible, phenomenal logical depths.

It's all about wonder here, or better it's all about wonder and pity,

for pity is the natural correlate of wonder.

There is something heartless at the heart of the real,

which does not respond to human petition,

and which makes it finally inscrutable to us.

Light enables sight, but an excess of it blinds.

That pity and wonder should go hand in hand is part of the general mystery.

The full title of this show is entitled "Epinions About Life and Literature."

Today we're going to talk about life in the primary biotic sense.

In particular, we are going to try to get into the most basic unit of the biotic,

namely the living cell.

I have with me in the studio a very special guest, Dr. Michael Hendrickson,

or Dr. Mike, as some of us like to call him.

Dr. Hendrickson is a professor of pathology in the Stanford Medical School

and co-director of the surgical pathology laboratory at the Stanford Medical Center.

His background is clinical and his research activities involve developing more effective histopathologic

or microscopic classifications for the management of cancer.

We'll be talking to him about that as well.

For cancer is the pity of life's wonder.

Dr. Mike, welcome to the program.

Thank you, glad to be here.

So, Michael, you would be surprised how poorly informed some of us are

when it comes to recent discoveries in the domain of biology.

So, I hope you don't mind if I start out by asking you some very basic questions.

I spoke earlier of life belonging to the order of the miraculous,

that is to say, of the extremely improbable.

To begin with, is it true that life on earth erupted from out of the inanimate?

Only once, a few billion years ago,

and that this singular event of spontaneous generation has never, ever been repeated

or recreated in the laboratory.

And if that's true, doesn't it mean at least two things.

First, that life is indeed an extreme improbability.

And second, that everything that is alive on earth today traces itself back to a common origin.

Well, as usual, the simple questions are the difficult ones.

And so, I'll do my best to provide an answer, actually in reverse order.

So, what I'll tackle first is the evidence that life did have a single origin.

And I think the strongest evidence for that, and I believe it to be true,

is that all organisms that we're familiar with from bacteria, up to humans,

share a common genetic code.

Now, the genetic code, as you'll recall, is a bit of cellular housekeeping machinery

that translates information in the DNA molecule, specifically in the nucleotide sequence of a DNA molecule,

into protein and other things that make us sell appear what it is.

It's structural components.

And so, that the genetic code is a translation manual that takes a codon or three nucleotides that are taken from an alphabet of four,

and translates those into amino acids, and the amino acids are 20 of them, so it's an alphabet of 20.

And what's interesting, and what really strongly suggests a one origin for least life that's currently present on the earth,

is that that code is remained invariant across extraordinarily diverse life forms.

This is up to some minor variations, but by and large, this rather complicated code is remained the same.

And I should add that to date, there are no compelling chemical reasons why it's that code rather than any of the infinite number of codes that it possibly could be.

So that's a strong bit of evidence.

The other is a kind of recent development.

Many of the listeners may be familiar with the evolutionary developmental biology of science that's exploded in recent decades.

This is an attempt to integrate basically embryologic facts into a unified count of evolution.

But those workers have discovered that they're set of highly conserved genes and their associated proteins that plan out the organism's body.

And what's become clear from their research is that this set of genes was present at the earliest time when life forms appear in the paleontologic record.

At that time those genes were in place, and they're in place in every organism that dates about a half a billion years ago on up to the present.

These are common genes. These are genes that are common to all these species.

So that animals basically were not talking about bacteria and so forth, but animals with organs and so forth.

The body plans of those animals is determined to a large extent by various permutations and combinations of the effects of these genes.

Well, in fact, I was reading the article in the New York Review of Books, the most recent issue, May 11th, I believe, on Evo Devo as it's called, or evolutionary development.

Where, in fact, I think what you're talking about there, I remember them speaking about Hox genes, for example, that control which, what do we have?

Like 25,000 genes in our bodies, each cell of our body will talk about that in a minute, but the idea of being that many of these genes lie dormant for the most part, and then they're activated in order to produce proteins or body parts and so.

The question is what activates or deactivates them? And it sounds like many of the sort of switch-like genes are held or in common across a whole wide variety of species, and that it's not so much a difference in genetic makeup as much as in the way in which certain genes are turned on or switched off that account for diversity.

Do I get that? I mean, it's a very crude.

No, that's that I think is exactly right, or it states the findings today.

It was thought before this movement began that for every novelty and evolution, a new gene would have to be created.

And what the very elegant studies of the Evo-Divo people have exposed is that genes are arranged in a kind of hierarchy so that they're structural genes, produce enzymes and produce, you know, carrot and proteins that make up skin and hair and so forth, and cell walls.

So there are structural genes, but in addition to that, it turns out there's a whole hierarchy of control genes that turn specific genes on and off, and it's this extensive and complex network of control genes that the Evo-Divo people have exposed.

And this, of course, for the puzzle of nembriology is how you get from one cell that basically has the appearance that it does. It's not differentiated as anything.

And in a very short period of time, you create an organism that fly, for example, with wings and antennas and got in heart and so forth, or circulatory system.

And how does that happen? And it was a complete mystery, I think, up until the past couple of decades. What sort of genetic controls were responsible for that carefully orchestrated progression from an undifferentiated cell to the very many stages, embryologic stages at embryologist studied in the 19th century and could deal with descriptively.

But how all of that came about? And the genes to which you refer, these, what we call the switching genes are kind of a toolbox of switching genes as one of the workers in this area is referred to them, are these highly conserved genes that basically set out the body plan and finer divisions of this hierarchy decide, for example, that a leg should be in this segment, and that leg should have a certain configuration rather than another possible configuration, which is in the next segment over.

So that there are sort of two pieces to that. One is what's been revealed is that as an egg develops into a larvae or whatever the progression is in the particular organism, that each cell is endowed with an exquisite set of coordinates, longitude, latitude, depth, and so forth. And what happens to that cell, its developmental history, depends entirely on its location.

And that's managed by turning on and off these various switching genes.

In fact, I have that article with me and one of the kind of summarizing statements is that evolution is largely the consequence of random mutations in genetic switches, genes remain intact, but under new patterns of control, their function is altered, complexity and variety are created, at least in part by combining the egg.

I thought of, well, two, one is language with a certain kind of finite amount of words, you can go on creating all sorts of diverse works. The other is a musical instrument. I don't know.

I could talk about the one that occurred to me.

I could talk about the piano, where there's no end of combinatorial possibilities.

But this is, I gather this is a real sort of discovery that the genes themselves can remain more or less intact and similar, but that evolution takes place in the switching mechanisms that trend them on and off.

We should back up just a little bit to say something about the genome.

For example, in the human, only about 1% of the DNA is coding material, makes proteins and structural things in housekeeping genes and so forth.

A smaller percentage is involved in producing regulatory proteins that's scurry around on the DNA and instruct, in a sense, decide what strips of DNA are going to be expressed in this particular cell in this particular location.

So that while it's true that mutation was thought before this era is completely random. There are mutations in structural genes. That's why people develop taste, disease, or cystic fibrosis and these other things.

What drives evolution are the mutations that occur in these very special specialized conserved genes.

It's like, I mean, you can think of it again, reverting to the piano, no matter for the music matter, for its changing keys at a particular seggan.

What are the initial observations that put people onto this are instructive? There are mutations that were referred to before as hopeful monsters will recognize this from our book that we've enjoyed together.

Nicholas Mosley, great novel hopeful monsters.

The father of the male protagonist in that book is modeled after Bateson, who was an Edwardian geneticist.

He was in the business of collecting monsters because he thought that evolution had to progress with big jumps that you get a monster and then that would somehow be advantaged.

That's how you got these big changes that were otherwise totally inexplicable with these small changes that were postulated by Darwin, which goes a name of gradualism.

He collected all these monsters.

He would have organisms that had, I don't know he had, but more recent instances of these kind of mutations would have a fruit fly, for example.

Instead of an antenna, it would have a leg coming out where the antenna should be.

It was that that put people onto the idea that mutations could have these dramatic amplified cascading effects.

It would be a single mutation that would have a certain genetic transmission, autosomal recessive, and well characterized by the geneticists, but it would have this dramatic structural change.

That's what got people prepared for a set of control genes that were more plausible candidates for the genes that get mutated and drive evolution.

Where does Bateson's theory, is that part of the history of science that led nowhere or was he onto something?

Well, I mean, it's gradualism still, the reigning Orthodoxy.

The sort of favorite whipping boy of the Evo Devo people is the hopeful monster, solitary evolution, that it requires that kind of mutation, that dramatic change with a leg coming out.

It requires that kind of change to explain evolution.

What has replaced that is this more nuanced interpretation, know that there are genes that are responsible for that mutation, and those animals are not viable.

It's very hard to navigate around and should have an antenna and you have a leg in its place.

But the deeper lesson is that, well, twofold, I suppose, the first is that one mutation can produce a dramatic morphologic change.

And the second is that those kinds of the homeotic mutations that are called, or a big chunk of a body, winds up someplace where it ought to be.

Those kinds of mutations are scattered across the animal kingdom.

And that's suggested that whatever was going on in these mutations, there was a very general process that wasn't confined to flies or whatever.

And in humans, the business of having an extra rib, for example, is an instance of a homeotic mutation, where that vertebra somehow got the wrong message and decided it was a rib bearing vertebra rather than one that doesn't have one.

Well, the more I read about evolution and the more I try to make sense of the theory of it that guides it, I think the phenomena of life are way out ahead of the explanatory theory.

The idea of random mutation is one that I know that there's a lot of evidence for it, but it still sounds like magic to me.

How you go from random mutation to this extraordinary planetitude of animal and plant forms and the visible world as we know it to have evolved through a mechanism of random genetic mutation, whether in the Hox genes or else without that.

I'm sure they're right, all the most intelligent people believe it, but I somehow...

That never guaranteed truth in the past.

The other thing is when you read more about what happens inside a living cell, while we can describe and observe it, it seems not to follow a clean set of laws, like the laws of physics.

In fact, a book of ours by Schrodinger called "What is life?" Schrodinger being a physicist who then turned to the phenomenon of life and he studied the laws of hereditary.

Whatever laws of life obeys, they are not the laws of physics.

Without law, but the laws of physics certainly can account for them.

Would you agree that we're still far away from having a set of stable laws by which we can understand the complexity of life as it takes place even inside a single cell?

I think that's probably true, but I don't take to be a hopeless task.

I mean, there's no question that one's first exposure to this strange world of the cell, of the mechanisms that seem to be working there, the attempts to get one's mind around what they could be up to and so forth.

In genders, a sense of alienation of wonder almost discomfort.

It takes me back to the first days in medical school.

One's used to oneself and thinking about oneself the way we do phenomenologically, and then all of a sudden to be introduced, most dramatically, just in a gross scale, is in the anatomy land, and see the various bits and pieces that get you going,

the muscles that make you move that are very thoughtful of the words that you're thought of, and so forth, the neuro-anatomy.

It's a deeply alien and a little queasy, but it's a kind of deuce that's kind of queasy feelings.

None of that strangeness disappears as you examine life on a smaller and smaller scale.

So I was reading a book by a mannered Smith who talks about this a bit, mentions the Cartesian body as a machine thought in the 17th century.

But then, next to that, I've thought of Leibniz that the man-made machines have the character that the parts stop at a certain level.

Divine machines, it's parts all the way down, mechanisms all the way down, and there's very much that sense, I think, in reading cell biology, sorting through the evo divo business.

It's deeply alien and peculiar.

In fact, in the middle ages, the definition of the body derived from aerosol was parts within parts within parts.

Now, he had it right as somebody thinks. So why don't we talk a little bit about the parts, Michael?

I gather that there's about a hundred trillion cells in the human body or something like that.

And first question is, why would there have to be so many?

And as we go through, down from the organism as a whole, down to the organs, and we get really to what we take to be, I said, the basic unit of the biotic,

which is the living cell. But of course, that's not quite exact either because the living cell is itself made of parts within parts within parts.

Exactly. And so, again, I said some of us are our might listeners, it's a literary talk show more than anything else.

So I'm not going to take anything for granted in terms of our knowledge of biology.

What is it? What are the main components of a cell?

Okay. So this is true, but this is true what you say about this cell. That was one of the major breakthroughs in biology.

It's sort of akin to the enunciation of the atomic theory. It has that same status.

And the odd thing was that this is only in 1830s, 1840s, that the cell was identified as the significant level of organization.

So the cell has a complex architecture in two senses.

What the first is just in terms of its parts, the machine parts within the machine parts and so forth.

And I think we've all seen cutaways in the popular press of a cell.

And as you zoom in on the cell, it becomes apparent that it's not homogeneous structure, I suppose. That's the first thing to say.

That it had a kind of low power of magnification. There's a conspicuous center part, which is the nucleus.

And that's embedded in a matrix of a jelly, cytoplasm, and is surrounded by a cell membrane that delimits that cell from other cells or from the outside world and single cell organisms and so forth.

But that is you as you zoom in closer, and I'm thinking of the powers of ten-book that some of you may have seen.

We gradually click on powers of ten magnification and things become different, larger and stranger.

If we do another power of ten switch, we notice that the nucleus has a fine structure.

And there's a lot of detail, a lot of distinguishable organs in the nucleus, and distinguishable organs in the cytoplasm.

Which are those organs in the nucleus?

I know the chromosomes reside in the nucleus, is that right?

Right, so the chromosomes, so that's the genome basically in a highly packaged form.

We can talk about that in a second. That has its own machines and things that are involved in exposing parts of it and concealing other parts.

There's also a nucleolus, which is another organ that's involved in various activities.

And there's all -- and the nucleus itself is just to focus on that part of the cell for a moment.

As you zoom in, higher in higher magnification, now we start seeing molecules, the nucleus is a kind of rainforest.

There's a tremendous amount of molecular activity buzzing around, control proteins moving here and there, unwindings of the DNA, and so forth, in response to cell signals and so forth.

So that highly structured organ, the nucleus, is taken by itself, that has a membrane that delimits it from the cytoplasm, but there's a lot of trafficking, obviously, that passes through that membrane to the cytoplasm.

The cytoplasm is populated by a dozen or so distinguishable organs, organelles, mitochondria of ribosomes.

These are the little machines that are involved in that translation process, taking the information in DNA and translating that into protein information basically.

There's an elaborate system of cell membranes that are involved in cells that are in the business of secreting something, whether it be hormones or enzymes.

All of this activity is located along these membranes, and there's a kind of a sort of highway system.

They constitute a kind of highway system. Molecules are targeted for various parts of that membrane. They're transported to the surface of the cell to be excreted through the cell membrane.

So the cytoplasm has a highly detailed structure.

And then the delimiting membrane, the cell membrane, has a basic structure of a kind of lipid or fatty interior, and then a lot of proteins on the outside that stud the membrane, and there are hundreds of different kinds of proteins and transport channels that carry molecules from the outside in or the other way around.

And that membrane constitutes the cell sensory system.

So we have site, we have hearing, we have touch, we have all these other things. Cells communicate through chemical messengers.

So there are receptors. All of those receptors that are embedded in this fatty membrane are receiving information from the cells around.

That cell, it's cellular neighbors.

I'm fascinated by this, we're speaking with Dr. Michael Hendrickson about what is life basically.

In an hour. It might be a double segment, but I have two parts we'll see how far we can get.

Everything that is a life seems to have some kind of delimiting boundary. If not a membrane, then some kind of border.

Why, what is a membrane? Why does a nucleus need to have a membrane? Why do cells have membranes? Are they there to protect, but they're also permeable at the same time? Why does life depend so heavily on these borders?

Well, this gets back to our mutual friend Schrodinger. The two elements that seem to be constitutive of life are metabolic issues and information transformation issues.

So, apparatus is to handle that. The metabolic issue is this.

Schrodinger puzzled, one of the things Schrodinger puzzled over was how is it you can achieve order in one place and in a world that's experiencing a heat death basically, entropy is constantly increasing.

How do you decrease entropy? And then the cell is a highly ordered structure obviously. How does that happen?

And so his thought, which sort of, they feel of non equilibrium thermodynamics, was this, that order could increase in an isolated part of the universe at the expense of disordered increasing elsewhere.

And to make long story short, one of the things that is required for that is a constant flux of mass and energy through a confined space.

So you need something to isolate that bit in which the order accumulates from the world in which the disorder is increasing.

So I think that just as a kind of basic principle, one requires that compartmentalization for this to work.

The role of the cell membrane goes far beyond that though, because as you suggest, the cell membrane is the interface. It's the skin of the cell.

It's the skin. It's the mouth. It's all of those orifices we have, but those functions are consolidated in this membrane.

So that if you look at the fine structure of a membrane, you'll see that there are little channels that selectively emit a particular kind of molecule, a glucose molecule or sodium or potassium or whatever.

So they're highly differentiated channels through which matter can pass from the outside inside.

There are sensors like tactile sensors, but there are chemical sensors in the instance of the case of the cell.

So it picks up signals from surrounding cells, hormone molecules, for example, or whatever they pass through, but other protein molecules.

So the cell membrane has very many functions, as you've been saying.

Here's another naive question, Michael. Are there empty spaces between cells in an organism or is it a chock-full of life?

Well, they're now empty space in the sense of air, except in your lungs, of course, but so there's always going to be fluid or something in between cells.

It kind of depends on what cells you're thinking about. If we take, say, heart cells are enmeshed in a kind of acellular scaffolding.

So they're struts and beams and whatnot that hold the cells together called collagen fibers.

So cells are embedded within that structured matrix that are all acellular items that are produced by cells, or specialized cells that make collagen and elaborate that framework.

So much of the shape of a cell, the arrangement of various cells into organized tissue, all of that is negotiated by the sca- or managed by the scaffolding.

So you were saying that there were two aspects of metabolic, and that's, you know, now I understand that's an excellent explanation for why if you buy and just photographs thesis that if you're going to have an increased order in a certain part of the universe, you can have to protect it, give it a boundary within which to happen.

That would be the metabolic, but then there's also the informational thing that you refer to, the second aspect, and that's where the cell's membrane is that which enables communication or clove information.

And therefore it separates but also puts into the cell into relation.

That's right, that's right. Well the nuclear membrane has that character.

So the nucleus is chiefly the repository of the genome in this very complicated architectural arrangement.

But as information is transcribed from the genome, it has to pass out into the cytoplasm to be translated into protein.

So the messenger RNA is read off the relevant DNA segment that passes through the nuclear membrane and then the ribosome takes that on along with a bunch of other complicated stuff to make a protein.

So there has to be traffic back and forth between cytoplasm and nucleus.

Also all of those elements that control the expression of the genome have to pass through signaling molecules have to pass through into the nucleus.

So it's a very busy interface between nucleus and cytoplasm.

The other odd thing about these organelles is in the side is that evolutionarily they're thought to be the sickening ultimate of parasitism and it says.

A mitochondria are in fact, are thought to be bacteria that have set up shop inside a cell eons ago that didn't have mitochondria.

And they enjoy this kind of symbiotic relationship to the extent that they have become part of what we regard as our cells.

But chloroplasts, the organelles that make plants green and photosynthesis occurs are also thought to be the kind of parasitism or...

Here's another mind-boggling thing for me is that every nucleus of every cell in anybody contains the totality of all the genes of that organism.

In our case something like 25,000, all within I suppose the chromosome within the nucleus.

A few years ago there was some... I don't know if it was a president of a university, probably not our university, but kind of alarmed at the ignorance that is taking hold regarding scientific matters.

I remember him saying something to the effect that I think every high school student should be able to tell us what is the difference between a gene and a chromosome.

I guess the first thing to be said is that bacterial cells and our cells are different and bacterial cells don't have a nucleus.

So that compartmentalization that we have in what I call eukaryotic cells doesn't exist in bacteria.

But in eukaryotic cells where there is a compartmentalization of genome from cytoplasm, the genetic endowment of the organism, and I've been referring to that as the genome,

there are several very long molecules of DNA in their associated protein, housekeeping, control elements.

And it's all of that in aggregates. You have your DNA, and all of that in aggregate, the histones, the proteins that surround the DNA and are involved in gene expression, all of that constitutes a chromosome.

So there is a fruit fly, for example, has four chromosomes.

So a gene turns out a gene is a little difficult to define.

So the Evelyn Foxe Keller has a nice book called The Century of the Gene that draws attention to some of these difficulties.

But the simplest version of the gene is that it's a strip of DNA that codes for something.

So people use gene for a coding gene. There are other strips of DNA that generate proteins that have to do with control, or there are bits of DNA that are upstream of a readable or a coding bit of DNA that control, through interactions, control the expression of that DNA.

But short answer, a gene is basically a coding bit of DNA. A chromosome houses huge numbers of one-fourth or one-twenty, one-twenty-third, or whatever of the organism's genes.

But the astonishing thing about the genome, I think, is that the vast majority of his non-coding, I think that was the surprise.

What does that mean exactly? Well, it means that if you just look at those genes that code for a specific protein, like p-moglobin, for example, or some of these channel proteins, one that's defective and cystic fibrosis are collagen.

If you look at the class of genes that produces some protein of that sort, it's some minuscule part, like one per cent or so of the total DNA content, is given over to producing that protein, genes that make those proteins.

The rest of it, as I mentioned before, at least some smaller part of it, is involved in coding genes.

And then there's a huge amount of so-called junk gene, or junk genetic material, that you always worry about people of characterizing something as junk, and before they've investigated all that.

But there are a lot of strips of DNA that used to be genes that have mutated, so they're non-functional, and so forth.

Anyway, most of the genome is made up of that kind of "dud" DNA, and so far as one knows.

I haven't read that book about the century of the gene, or what it would have used to refer to.

But would it be fair to say that in contemporary biology, there is such a kind of genocentric attitude, where if we can just figure out what gene does what, we can get the answer to the whole story.

And is there not also recently, I was looking at the review of this book called "The Possibility of Life," where certain biologists are reminding us that a gene can never function in isolation.

It's in relation to other genes in relation to the living cell. The cell is part of a larger sort of fabric of life, and then you have organs and organism.

The organism, it doesn't end at the organism because the organism is in relation to the environment.

This sort of reductionism is there a dangerous danger of a certain kind of reductionism in certain types of biology today, where the presupposition is that if we can just decode the gene, then we have the answer to the totality.

Forgetting that the totality is a totality of interrelations.

Yeah, I mean, that's completely true.

The late Stephen J. Gould referred to that as beanbag genetics.

There are a bunch of genes rattling around. Another term is a trait unculus.

The lying inside the genome is a kind of exact version of the trait, like blue eyes or get high sat-tasks scores or whatever.

That's actually a whole bunch of e-mail.

I don't know of any serious worker in the field who believes any of that.

I think that's Fox Keller's point, I think, is that there's a terrific lag between what sort of cutting edge genetic research is involved in the conceptual models that these folks are dealing with and what appears in the popular press.

That gets me back, I think, to the complexity of the cell. Let me just make one more point about that.

We talked about the anatomic complexity that there are organs and organs and organs, and so for the structural features.

The other thing that's become apparent is that in terms of metabolic and synthetic pathways, in terms of how a molecule of food is transformed into a bit of DNA or an amino acid building blocks for a

synthetic processes for these macromolecules, that the pathways that control the passage of matter through the cell are bio networks are highly complex.

There's a parallel set of pathways that have to do with control taking signals from the stimulation of the cell's sensory surfaces and translating that into a cell action of some sort of secretion, a move-met or whatever.

Those networks are highly nonlinear. They have a kind of architecture that is important as the particular elements that comprise the nodes in that network.

This all gets around the business of trying to track a particular genetic input into a particular phenotypic output.

There are a few things where that sort of works, like TASACs disease, where a genetic abnormality is a kind of trump card.

It doesn't make any difference. What other genes are on board? That's such a fatal hit that the organism is not going to make.

The child is not going to make it.

Other things like hypertension or these complex genetic abnormalities are mediated by what you might think of as a kind of integrated circuit.

There are a lot of genetic inputs to that circuit, and then there's a kind of phenotypic output, high blood pressure, whatever.

It's kind of like trying to track on where your tax dollar went. Did it go into this bolt on this plane or whatever?

That there's that same kind of scrambling integration that occurs. It makes it a nonsense to talk about the gene for any particular trait in general.

One of the great things about having a radio show on KZSU, Michael, is that you can get a signal from the producer saying, "You have been cleared to have a second hour of this discussion."

The great thing is that I'm my own producer. I am here by declare that we are going to continue this conversation into a second hour.

We'll be right back with Dr. Michael Hendrickson.

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