One to make you happy, one to make you sad, one to make you mad--is that really the way your genes work?
Well, these last six months have been an exciting time for the sheep named
Dolly, ever since it was revealed that she
was the first mammal cloned from adult cells. There was the night she spent
in the Lincoln bedroom and the photo op
with Al Gore; the triumphant ticker-tape parade down Broadway, the billboard
ads for Guess Genes. Throughout the
media circus, Dolly has been poised, patient, cordial, and even-tempered--the
epitome of what we look for in a
celebrity and role model. But despite her charm, people keep saying mean
things about Dolly. Heads of state,
religious leaders, and editorialists fall over themselves in calling her
an aberration of nature and an insult to the sacred
biological wonder of reproduction. They thunder about the anathema of even
considering applying to humans the
technology that spawned her.
What’s everyone so upset about? Why is cloning so disturbing? Clearly,
it’s not the potential for droves of clones
running around with the exact same renal filtration rate that has everyone
up in arms. It’s probably not even the threat
of winding up with a bunch of clones who look identical, creepy though
that would be. No, the real horror is the
prospect of having multiple copies of a single brain, with the same neurons
and the same genes directing those
neurons, one multibodied consciousness among the clones, an army of photocopies
of the same soul, all thinking,
feeling, and acting identically.
Fortunately, that can’t happen, as people have known ever since scientists
discovered identical twins. Such individuals
constitute genetic clones, just like Dolly and her “mother”--the sheep
from which the original cell was taken. Despite
all those breathless stories about identical twins separated at birth who
flush the toilet before using it, twins are not
melded in mind, do not behave identically. For example, if an identical
twin is schizophrenic, the sibling, with the
identical “schizophrenia gene(s),” has only about a 50 percent chance of
having the disease.
A similar finding comes from a fascinating experiment by Dan Weinberger
of the National Institute of Mental Health.
Give identical twins a puzzle to solve and they might come up with closer
answers than one would expect from a pair
of strangers. While they’re working on the puzzle, however, hook the twins
up to a pet scanner, a brain-imaging
instrument that visualizes metabolic demands in different regions of the
brain. You’ll find the pattern of activation in
the pair differing considerably, despite the similarity of their solutions.
Or use an mri to get some detailed pictures of
the brains of identical twins and start measuring stuff obsessively--the
length of this part, the width of that, the volume
of another region, and the surface area of the cortex--and those identical
twins with their identical genes never have
identical brains. Every measure differs.
The careful editorialists have made this point. Nonetheless, that business
about identical genes producing identical
brains tugs at a lot of people. Gene-behavior stories are constantly getting
propelled to the front pages of newspapers.
One popped up shortly before Dolly, when a team of researchers reported
that a single gene, called fru, determines the
sexual behavior of male fruit flies. Courtship, opening lines, foreplay,
who they come on to--the works. Mutate that
gene and--get this--you can even change the sexual orientation of the fly.
What made the story front-page news, of
course, wasn’t our insatiable fly voyeurism. “Could our sexual behaviors
be determined by a single gene as well?”
every article asked. And a bit earlier, there was the hubbub about the
isolation of a gene related to anxiety in humans,
and shortly before that, a gene related to novelty- seeking behavior, and
a while before that, a gene whose mutation in
one family was associated with violent antisocial behavior, and before
that. . .
Why do these stories command attention? For many, genes and the DNA they
contain represent the holy grail of
biology, the code of codes (two phrases often used in lay discussions of
genetics). The worship at the altar of the gene
rests on two assumptions. The first concerns the autonomy of genetic regulation:
it is the notion that biological
information begins with genes--dna is the commander, the epicenter from
which biology emanates. Nobody tells a
gene what to do; it’s always the other way around. The second assumption
is that when genes give a command,
biological systems listen. Genes, the story goes, instruct your cells as
to their structure and function. And when those
cells are neurons, their functions include thought, feelings, and behavior.
Thus, the gene worshipers believe, we are
finally identifying the biological factors that make us do what we do.
A typical example of the code-of-codes view recently appeared in a lead
New Yorker article by Louis Menand, an
English professor at the City University of New York. Menand ruminates
on anxiety genes, when “one little gene is
firing off a signal to bite your fingernails” (there’s that first assumption--autonomous
genes firing off whenever
some notion pops into their heads). He asks himself how we can reconcile
societal, economic, and psychological
explanations of behavior with those ironclad genes. “The view that behavior
is determined by an inherited genetic
package” (there’s the second assumption--genes as irresistible commanders)
“is not easily reconciled with the view
that behavior is determined by the kinds of movies a person watches.” And
what is the solution? “It is like having the
Greek gods and the Inca gods occupying the same pantheon. Somebody’s got
to go.”
In other words, if you buy into the notion of genes firing off and determining
our behaviors, such modern scientific
findings are simply incompatible with the environment having an influence.
Something’s gotta go.
Now, I’m not sure what sort of genetics they teach in Menand’s English
department, but the something’s-gotta-go
loggerhead is what most behavioral biologists have been trying to unteach
for decades, apparently with limited
success. Which is why it’s worth another try.
Okay. You’ve got nature--neurons, brain chemicals, hormones, and of course,
at the bottom of the cereal box, genes.
And then there’s nurture, all those environmental breezes gusting about.
Again and again, behavioral biologists insist
that you can’t talk meaningfully about nature or nurture, only about their
interaction. But somehow people can’t seem
to keep that thought in their heads. Instead, whenever a new gene is trotted
out that “determines” a behavior by
“firing off,” they see environmental influences as the irrelevant something
that has to go. Soon poor, sweet Dolly is a
menace to our autonomy as individuals, and genes are understood to control
who you go to bed with and whether you
feel anxious about it.
Let’s try to undo the notion of genes as neurobiological and behavioral
destiny by examining those two assumptions,
beginning with the second one--that cells, including those in our heads,
obey genetic commands. What exactly do
genes do? A gene, a stretch of DNA, does not produce a behavior. A gene
does not produce an emotion, or even a
fleeting thought. It produces a protein. Each gene is a specific DNA sequence
that codes for a specific protein. Some
of these proteins certainly have lots to do with behavior and feelings
and thoughts; proteins include some hormones
(which carry messages between cells) and neurotransmitters (which carry
messages between nerve cells); they also
include receptors that receive hormonal and neurotransmitter messages,
the enzymes that synthesize and degrade those
messengers, many of the intracellular messengers triggered by those hormones,
and so on. All those proteins are vital
for a brain to do its business. But only very rarely do things like hormones
and neurotransmitters cause a behavior to
happen. Instead they produce tendencies to respond to the environment in
certain ways.
To illustrate this critical point, let’s consider anxiety. When an organism
is confronted with a threat, it typically
becomes vigilant, searches for information about the nature of the threat,
and struggles to find an effective coping
response. Once it receives a signal indicating safety--the lion has been
evaded, the traffic cop buys the explanation and
doesn’t issue a ticket--the organism can relax. But that’s not what happens
with an anxious individual. Instead this
person will skitter frantically among coping responses, abruptly shifting
from one to another without checking
whether anything has worked. He may have a hard time detecting the safety
signal and knowing when to stop his
restless vigilance. Moreover, the world presents a lot of triggers that
not everyone reacts to. For the anxious individual,
the threshold is lower, so that the mere sight of a police car in the rearview
mirror can provoke the same storm of
uneasiness as actually being stopped. By definition, anxiety makes little
sense outside the context of what the
environment is doing to an individual. In that framework, the brain chemicals
and genes relevant to anxiety don’t make
you anxious. They make you more responsive to anxiety-provoking situations,
make it harder to detect safety signals.
The same theme continues in other behaviors as well. The exciting (made-of-protein)
receptor that apparently has to
do with novelty-seeking behavior doesn’t actually make you seek novelty.
It makes you more pleasurably excited than
folks without that receptor variant get when you happen to encounter a
novel environment. And those (genetically
influenced) neurochemical abnormalities of depression don’t make you depressed.
They make you more vulnerable to
stressors in the environment, to deciding that you are helpless even when
you’re not.
One might retort that in the long run we are all exposed to anxiety-provoking
circumstances, all exposed to the
depressing world around us. If we are all exposed to those same environmental
factors but only the people who are
genetically prone to depression get depressed, that is a pretty powerful
vote for genes. In that scenario, the “genes
don’t cause things, they just make you more sensitive to the environment”
argument becomes empty and semantic.
The problems here, however, are twofold. First, a substantial minority
of people with a genetic legacy of depression do
not get depressed, and not everyone who has a major depression has a genetic
legacy for it. Genetic status is not all
that predictive by itself. Second, we share the same environments only
on a very superficial level. For example, the
incidence of depression (and its probable biological underpinnings) seem
to be roughly equal throughout the world.
However, geriatric depression is epidemic in our society and far less prevalent
in traditional societies in the developing
world. Why? Different societies produce remarkably different social environments,
in which old age can mean being a
powerful village elder or an infantilized has-been put out to a shuffleboard
pasture.
The environmental differences can be more subtle. Periods of psychological
stress involving loss of control and
predictability during childhood may well predispose one toward adult depression.
Two children may have had similar
childhood lessons in “there’s bad things out there that I can’t control”--both
may have seen their parents divorce,
lost a grandparent, tearfully buried a pet in the backyard, faced the endless
menacing of a bully. Yet the temporal
pattern of their experience is unlikely to be identical, and the child
who experiences all those stressors over a one-year
period instead of over six years is far more likely to come with the cognitive
distortion, “There’s bad things out there
that I can’t control and, in fact, I can’t control anything,” that sets
you up for depression. The biological factors that
genes code for in the nervous system typically don’t determine behavior.
Instead they affect how you respond to often
very subtle influences in the environment. There are genetic vulnerabilities,
tendencies, predispositions--but rarely
genetic inevitabilities.
Now let’s go back to that first assumption about behavioral genetics--that
genes always have minds of their own. It
takes just two startling facts about the structure of genes to blow this
one out of the water.
A chromosome is made of DNA, a vastly long string of it, a long sequence
of letters coding for genetic information.
People used to think that Gene 1 would comprise the first eleventy letters
of the DNA message. A special letter
sequence would signal the end of that gene, the next eleventy and a half
letters would code for Gene 2, and so on,
through tens of thousands of genes. Gene 1 might specify the construction
of insulin in your pancreas; Gene 2 might
specify protein pigments that give eyes their color; and Gene 3, active
in neurons, might make you aggressive. Ah,
caught you: might make you more sensitive to aggression-provoking stimuli
in the environment. Different people have
different versions of Genes 1, 2, and 3, some of which work better than
others. An army of biochemicals do the scut
work, transcribing the genes, reading the DNA sequences, and following
the instructions they contain for constructing
the appropriate proteins.
As it turns out, that’s not really how things work. Instead of one gene
coming immediately after another, with the
entire string of DNA devoted to coding for different proteins, there are
long stretches of DNA that don’t get
transcribed. Sometimes those stretches even split up a gene into subsections.
Some of the nontranscribed, noncoding
DNA doesn’t seem to do anything. It may have some function that we don’t
yet understand, or it may have none at
all. But some of the noncoding DNA does something very interesting indeed.
It’s the instruction manual for how and
when to activate genes. These stretches have many names--regulatory elements,
promoters, responsive elements.
Various biochemical messengers may bind to each of them, altering the activity
of the gene immediately
“downstream”-- immediately following it in the string of DNA.
Far from being autonomous sources of information, then, genes must obey
other factors that regulate when and how
they function. Very often, those factors are environmental. For example,
suppose something stressful happens to a
primate. A drought, say, forces to it forage miles each day for food. As
a result, the animal secretes a stress hormone,
cortisol, from its adrenals. Cortisol molecules enter fat cells and bind
to cortisol receptors. These hormone-receptor
complexes find their way to the DNA and bind to a regulatory stretch of
DNA. Whereupon a gene downstream is
activated, which produces a protein, which indirectly inhibits that fat
cell from storing fat. It’s a logical thing to
do--while starving and walking the grasslands in search of a meal, the
primate needs fat to fuel muscles, not to laze
around in fat cells.
In effect, regulatory elements introduce the possibility of environmentally
modulated if-then clauses. If the
environment is tough and you’re working hard to find food, then make use
of your genes to divert energy to
exercising muscles. The environment, of course, doesn’t mean just the weather.
The biology is essentially the same if
a human refugee travels miles from home with insufficient food because
of civil strife. The behavior of one human can
change the pattern of gene activity in another.
Let’s look at a fancier example of how environmental factors control the
regulatory elements of DNA. Suppose that
Gene 4037 (not its real name--it has one, but I’ll spare you the jargon),
when left to its own devices, is
transcriptionally active, generating its protein. However, as long as a
particular messenger binds to a regulatory
element that comes just before 4037 in the DNA string, Gene 4037 shuts
down. Fine. Now suppose that inhibitory
messenger happens to be very sensitive to temperature. In fact, if the
cell gets hot, the messenger goes to pieces and
comes floating off the regulatory element. Freed from the inhibitory regulation,
Gene 4037 will suddenly become
active. Maybe it’s a gene that works in the kidney and codes for a protein
relevant to water retention. Boring--another
metabolic story, this one having to do with how a warm environment triggers
metabolic adaptations that stave off
dehydration. But suppose, instead, Gene 4037 codes for an array of proteins
that have something to do with sexual
behavior. What have you just invented? Seasonal mating. Winter is waning,
each day gets a little warmer, and in
relevant cells in the brain, pituitary, or gonads, genes like 4037 are
gradually becoming active. Finally some threshold
is passed and, wham, everyone starts rutting and ovulating, snorting and
pawing at the ground, and generally carrying
on. (Actually, in most seasonal matters, the environmental signal for mating
is the amount of daily light exposure, or
the days are getting longer, rather than temperature, or the days are getting
warmer. But the principle is the same.)
Here’s a final, elegant example. Every cell in your body has a distinctive
protein signature that marks it as yours.
These “major histocompatability” proteins allow your immune system to tell
the difference between you and some
invading bacterium--that’s why your body will reject a transplanted organ
with a very different signature. When those
signature proteins get into a mouse’s urine, they help make its odor distinct.
For a rodent, that’s important stuff.
Design receptors in olfactory cells in a rodent’s nose that can distinguish
signature odorant proteins similar to its own
from totally novel ones. The greater the similarity, the tighter the protein
will fit into the receptor. What have you just
invented? A way to distinguish between the smells of relatives and strangers--something
rodents do effortlessly.
Keep tinkering with this science project. Now couple those olfactory receptors
to a cascade of chemical messengers
inside the cell, one messenger triggering the next until you get to the
DNA’s regulatory elements. What might you
want to construct? How about: If an olfactory receptor binds an odorant
indicating the presence of a relative, then
trigger a cascade that ultimately inhibits the activity of genes related
to reproduction. You’ve just invented a
mechanism by which animals could avoid mating with close relatives. Or
you can construct a different cascade: if an
olfactory receptor binds an odorant indicating a relative, then inhibit
genes that are normally active and that regulate the
synthesis of testosterone. There you have a means by which rodents get
bristly and aggressive when a strange male
stinks up their burrow but not when the scent belongs to their kid brother.
In each of these examples you can begin to see the logic, an elegance that
teams of engineers couldn’t do much to
improve. And now for the two facts about this regulation of genes that
will dramatically change your view of them.
First, when it comes to mammals, by the best estimates available, more
than 95 percent of DNA is noncoding.
Ninety-five percent. Sure, a lot of it may have no function, but your average
gene comes with a huge instruction
manual for how to operate it, and the operator is very often environmental.
With a percentage like that, if you think
about genes and behavior, you have to think about how the environment regulates
genes and behavior.
The second fact involves genetic variation between individuals. A gene’s
DNA sequence often varies from person to
person, which often translates into proteins that differ in how well they
do their job. This is the grist for natural
selection: Which is the most adaptive version of some (genetically influenced)
trait? Given that evolutionary change
occurs at the level of DNA, “survival of the fittest” really means “reproduction
of individuals whose DNA sequences
make for the most adaptive collection of proteins.” But--here’s that startling
second fact--when you examine
variability in DNA sequences among individuals, the noncoding regions of
DNA are considerably more variable than
are the regions that code for genes. Okay, a lot of that variability is
attributable to DNA that doesn’t do much and so
is free to drift genetically over time without consequence. But there seems
to be a considerable amount of variability in
regulatory regions as well.
What does this mean? By now, I hope, we’ve gotten past “genes determine
behavior” to “genes modulate how one
responds to the environment.” The business about 95 percent of DNA being
noncoding should send us even further,
to “genes can be convenient tools used by environmental factors to influence
behavior.” And that second fact about
variability in noncoding regions means that it’s less accurate to think
“evolution is about natural selection for
different assemblages of genes” than it is to think “evolution is about
natural selection for different sensitivities and
responses to environmental influences.”
Sure, some behaviors are overwhelmingly under genetic control. Just consider
all those mutant flies hopping into the
sack with insects their parents disapprove of. And some mammalian behaviors,
even human ones, are probably pretty
heavily under genetic regulation as well. These are likely to code for
behaviors that must be performed by everyone in
much the same way for genes to be passed on. For example, all male primates
have to go about the genetically based
behavior of pelvic thrusting in fairly similar ways if they plan to reproduce
successfully. But by the time you get to
courtship, or emotions, or creativity, or mental illness, or any complex
aspect of our lives, the intertwining of biological
and environmental components utterly defeats any attempt to place them
into separate categories, let alone to then
decide that one of them has got to go.
I’m a bit hesitant to reveal the most telling example of how individuals
with identical genes can nonetheless come up
with very different behaviors, as I have it thirdhand through the science
grapevine, and I’ll probably get some of the
details wrong. But what the hell, it’s such an interesting finding. It
concerns the very extensive opinion poll that was
carried out among sheep throughout the British Isles. Apparently, the researchers
managed to get data from both
Dolly and her gene-donor mother. So get a load of this bombshell: Dolly’s
mother voted Tory, listed the Queen Mum
as her favorite royal, worried about mad cow disease (“Is it good or bad
for the sheep?”), enjoyed Gilbert and
Sullivan, and endorsed the statement, “Behavior? It’s all nature.” And
Dolly? Votes Green Party, thinks Harry and
William are the cutest, worries about “the environment,” listens to the
Spice Girls, and endorsed the statement,
“Behavior? Nature. Or nurture. Whatever.” You see, there’s more to behavior
than just genes.