https://www.nybooks.com/articles/2019/03/07/carl-zimmer-twisted-dna/
Our Twisted DNA
Tim Flannery <https://www.nybooks.com/contributors/tim-flannery/>
March 7, 2019 Issue <https://www.nybooks.com/issues/2019/03/07/>
She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of
Heredity
<https://www.amazon.com/gp/product/1101984597?ie=UTF8&tag=thneyoreofbo-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=1101984597>
by Carl Zimmer
Dutton, 657 pp., $30.00
<https://cdn.nybooks.com/wp-content/uploads/2019/02/flannery_1-030719.jpg>Museum
of Modern Art, New York/Art Resource/© 2019 Banco de México Diego Rivera
Frida Kahlo Museums Trust, Mexico, D.F./Artists Rights Society (ARS), New
York
Frida Kahlo: *My Grandparents, My Parents, and I (Family Tree)*, 1936
Tracing genealogies has become immensely popular of late, and numerous
companies offer to help you search through historical records or analyze
your DNA. The pastime is no doubt enlivened by the scintillating
possibility that you might discover noble blood, or even a notorious rogue,
hiding in your family tree. But such discoveries generally don’t tell the
searcher much; most of us have little idea of how our genes are bequeathed
to us at all.
Carl Zimmer’s interest in genetic inheritance began when his wife, Grace,
was pregnant with their first child, and the couple met with a genetics
counselor. Zimmer, who has written books on evolution, neuroscience, and
bacteriology, didn’t see the point of the meeting, for they had already
decided to have the child regardless of any genetic flaws that might be
found. It was only when the counselor asked the couple about their family
histories that Zimmer realized how little he knew about his own, and began
to be curious about his ancestry.
The result, many years later, is both two delightful, healthy
daughters and *She
Has Her Mother’s Laugh*, a grand and sprawling book that investigates all
aspects of inheritance, from ancient Roman law to childhood learning, and
on to the bacteria that inhabit our belly buttons (which are surprisingly
varied among individuals). Along the way, the book provides many amusing
historical anecdotes and important scientific insights.
Inheritance, as a means of endowing privilege, has been of vital importance
to people ever since the Neolithic period some ten thousand years ago.
Pedigrees (from *pé de grue*, the foot of a crane, which resembles the
connecting lines on ancestral trees) have long been used to justify social
hierarchies. In times past, the European nobility would spend lavishly to
draw up impressive (and often invented) pedigrees for themselves.
In 1715 the Irish noble Viscount Mountcashel published a pedigree in which
he claimed to be able to trace his ancestry all the way back to Adam and
Eve. In Mountcashel’s time, the popular understanding of heredity didn’t
extend much beyond the theory that men planted seeds in the wombs of women,
where they were nurtured. Yet it does seem odd for Mountcashel to have
averred that, in all the ages since Adam, not one of his female ancestors
had ever become pregnant by anyone but her wedded partner. “Son of a bitch”
is such a powerful insult not just because it slanders one’s mother, but
because it questions one’s pedigree, and therefore the legitimacy of one’s
position and inheritance.
If you are searching for your own noble blood, genetic research has both
good and bad news for you. If you follow a pedigree, with all its forkings,
back to the eighth century, you will trace over a trillion forks—an
impossibility, because that is more than the number of people that have
ever existed. When Joseph Chang developed the first statistical model of
heredity in 1999 to explain the paradox, he established that many forks
disappeared if our ancestors were closely related to one another, and that
if you go back seven thousand years, “you reach a point in time when all
the individuals who have *any* descendants among living people are
ancestors of *all* living people.” So you might have pharaohs in your
ancestry, and possibly caesars and Holy Roman emperors as well. Yet because
of the swapping of DNA fragments during sexual reproduction, the DNA of our
ancestors becomes diluted very quickly. Only 1 percent or less of an
ancestor who lived four centuries ago is present in your DNA.
None of this, of course, was understood before the discovery of DNA in the
1950s. Early misconceptions about ancestry, along with a belief in superior
breeds, were expressed in the eugenics movement in the late nineteenth
century. In 1910 Henry Goddard, an American high school teacher turned
psychologist, invented the word “moron” to describe people with mental
deficiencies. He was director of research at the Vineland Training School
in New Jersey, which had been established to care for “feeble-minded” boys
and girls. He believed that “degeneracy,” in the form of children with
special needs, was increasing. The deputy principal of the school argued
that “we must stop the increase. And that means to find out where they come
from, why they come and what to do to check the stream.”
Goddard soon convinced himself that moronism was an inherited condition,
and he wrote a book about the delinquent ancestry of Emma Wolverton, one of
the wards at the Vineland School, giving her the pseudonym Deborah Kallikak
(from the Greek for “good” and “bad”). His best-selling book *The Kallikak
Family*, published in 1912, propelled him to fame and remained influential
well into the 1950s. It had made an impression on Hitler in the 1920s and
informed the Reich’s racial hygiene laws, under which feeble-minded
children and other “undesirable types” were sterilized or euthanized.
Goddard’s argument that feeble-mindedness was passed down from generation
to generation turned out to be entirely spurious. In the 1980s two
genealogists reexamined the Wolverton (Kallikak) family tree as given by
Goddard and discovered that Emma Wolverton’s supposed pedigree was as false
as Mountcashel’s claim of descent from Adam.
Fraud and error have been an ongoing theme among those interested in
establishing the genetic basis of intelligence. When the British
psychologist Cyril Burt published a series of studies of identical twins,
he convinced many that intelligence was determined by inheritance. But in
1966 the Princeton psychologist Leon Kamin read Burt’s work and “within ten
minutes…knew…that it just had to be fake.” The test scores given for
identical twins were correlated to within a tenth of a percent: one such
instance would be unlikely, but the twenty instances in Burt’s study were
“astronomically improbable.” Not only had Burt invented his research
findings, he’d published scientific papers under false names to give the
impression that other researchers supported his work.
Although Burt gave twin studies a bad name, other more honest researchers
persisted in the field. They have established that about half of the
variation in intelligence test scores can be attributed to inheritance,
though just which genes are responsible remains a puzzle. As Zimmer says:
While identical twins often end up with similar test scores, sometimes they
don’t. If you get average scores on intelligence tests, it’s entirely
possible your children may turn out to be geniuses. And if you’re a genius,
you should be smart enough to recognize your children may not follow suit.
The nongenetic factors that bear upon intelligence are important because
they can be influenced by technology and social policies. The introduction
of iodine into salt in the US, for example, raised the average IQ by 3.5
points (because iodine is vital for the production of some growth hormones,
even a mild deficiency during pregnancy can impede fetal brain
development). Poverty, meanwhile, can dumb us down: studies show that
although living in poverty does not reduce the heritability of intelligence
in Europe, in the US it does. Could it be that the existence in Europe of
universal health care and more generous social programs is protecting the
intelligence of its most vulnerable citizens?
Some of the most fascinating material Zimmer covers concerns the phenomena
of mosaicism and chimerism, in which individuals are made up of cells with
differing genetic inheritances. Mosaicism can occur in a number of ways.
For example, if a genetic mutation arises in a cell early in development,
the descendants of that cell will make up a large proportion of the cells
present in the adult. One outcome is a skin disorder known as CHILD, in
which half of a person’s body is darkly pigmented, while the remainder is
pale. Cancer is a kind of mosaicism that often arises later in life, when
some genetic mutation allows a cell and its descendants to grow in an
uncontrolled manner.
Chimerism (from the Greek word for a mythological monster whose body is
composed of parts from different animals) is an even more intriguing
condition. Chimeric individuals are composed of cells originating from two
or more separate origins. The term “genetical chimera” was first coined by
Sir Peter Medawar, who used it to describe freemartins, female cattle that
shared cells in the uterus with a male twin, and whose cellular makeup
therefore includes both male (from the bull calf) and female cells.
Medawar’s pioneering studies of chimeras and immune tolerance led to
breakthroughs in organ transplantation. He was also involved in the
discovery of the first human to be recognized as a chimera. Known today
only as “Mrs. McK,” she was twenty-five years old in 1953, when she decided
to donate blood. When her blood sample was analyzed, it was discovered to
consist of both A and O types. A baffled doctor wondered if she had
recently had a blood transfusion. But Mrs. McK had not had one, so the
doctor sent a blood sample to an expert in London, who thought to ask her
if she had a twin. Mrs. McK replied that she had a twin brother, but that
he had died when he was three months old. Her type A blood cells were all
that remained of him. Medawar, in describing the case, wrote:
There is no telling how long Mrs McK will remain a chimera, but she has now
been so for twenty-eight years; probably, in the long run, her twin
brother’s red blood cells will slowly disappear, and so pay back the still
outstanding balance of his mortality.
Other kinds of chimeras are even more astonishing than those only
detectable by blood tests. A baby born in a Seattle hospital in 1960 had a
clitoris so large that it resembled a penis. When she was two years old she
was operated upon to reduce the size of the organ. But after the removed
tissue was examined, some cells were found to be genetically male. Further
tests revealed that her entire body was a mixture of male and female cells.
The child was the result of two eggs that had been fertilized by different
sperm—one with male chromosomes, the other with female. Normally the result
would have been twins, a boy and a girl. But the fertilized eggs had fused,
creating a single chimeric individual.
Such phenomena illustrate the multifariousness of inheritance: we can be
stitched together, from a genetic perspective, in ways that complicate our
understanding of what an individual is. Unsurprisingly, the law is poorly
equipped to deal with such nuances. In 2003 Lydia Fairchild, a pregnant,
single mother of three living in Washington State, sought welfare benefits.
In order to qualify she had to take a DNA test to prove that she and her
former partner were indeed the parents of their children. The tests proved
paternity but, according to the Department of Social Services, showed that
Fairchild could not possibly be the mother of her children.
Suspecting abduction or a child surrogacy scam, the court put Fairchild’s
children in foster care and charged her with fraud. A court officer was
present to witness the birth of her fourth child, but even that was not
persuasive; only DNA would be accepted as evidence of the child’s
maternity. Even Fairchild’s father, dazzled by science, began to have
doubts about his daughter’s honesty. Thankfully, her lawyer recalled an
earlier, similar case that had resulted from chimerism. Through sheer good
fortune a hospital had kept a cervical smear taken years earlier, and
analysis of the sample revealed that the cells of Fairchild’s body were
derived from two genetically distinct female eggs that had fused to form
one individual. Her sex cells came from one egg, while the parts of her
body used in the DNA test came from the other. The court was finally
convinced, and Fairchild’s children were returned to her, but not before
severely traumatizing the family. As we contemplate the potentially dire
consequences of the case, the fact that supposed scientific evidence is so
persuasive that eyewitness testimony, and even the love of a parent, could
be negated by it should act as a caution.
Chimeras can also result from pregnancy. Cells from embryos regularly cross
via the placenta into the mother during gestation, while her cells can end
up in the embryo. It is astonishing how long such cells can survive. One
woman who had given birth to a son still had cells with Y-chromosomes in
her body twenty-seven years later. In another case, an entire lobe of a
woman’s liver that had been damaged by disease was repaired by fetal cells
that remained in her body after an abortion. A mother’s brain cells, too,
can be derived from offspring.
<https://cdn.nybooks.com/wp-content/uploads/2019/02/flannery_2-030719.jpg>Émilie
Regnier: *Maternal Bloodlines* (detail), 2018. ‘DNA is drawing a
self-portrait through the people who are genetically related to me,’
Regnier writes. ‘This series of work is my way to reconcile the past by
creating my own family album. It’s a story of the reappropriation of my own
history, recognizing the figures in my maternal and paternal families, and
consolidating the two branches of my polarizing entities: the black and the
white, the Haitian and the Canadian.’
As long as chimeras and mosaics were detected on the basis of physical
manifestations or blood type, they were considered to be phenomenally
rare—indeed freakish. By 1983, only seventy-five cases of human chimeras,
as detected from blood type, were known, while mosaicism was mostly known
from medical cases. Joseph Merrick, the “Elephant Man,” suffered from a
form of mosaicism known as Proteus syndrome, which left parts of his body
deformed by monstrous growths, while other parts remained completely
normal. For decades, his sad example defined the condition for many.
Recent advances in genetic analysis have revealed that chimerism is common.
In fact, chimeric individuals may be the rule, rather than the exception,
among mammals. One Danish study of the blood of 154 girls aged ten to
fifteen discovered that around 13 percent of them had blood cells with
Y-chromosomes. These cells probably originated from an older brother and
had crossed into the mother, where they survived before crossing into, and
taking root in, the daughter. A Seattle study of fifty-nine women who died,
on average, in their seventies found that 63 percent had cells with
Y-chromosomes in their brains.
As bizarre as chimeras might seem, they represent only the surface waters
of Zimmer’s deep dive into the nature of inheritance. Epigenetics, a
fast-expanding area of science that explains how things experienced by
individuals can influence the traits that are inherited by their offspring,
seems to contradict our conventional understanding of genetics. The
epigenome, “that collection of molecules that envelops our genes and
controls what they do,” as Zimmer puts it, operates through methylation—the
process whereby methyl-group molecules are added to the molecular envelope
surrounding the DNA, and so inhibit certain genes from operating (and, in
some cases, from operating in descendants as well).
We owe one of the most penetrating insights into epigenetics to a
laboratory accident. Michael Skinner of Washington State University was
examining the impact of the anti-fungal agent vinclozolin on laboratory
rats. He discovered that the offspring of rats exposed to the chemical
produced deformed sperm. When a laboratory assistant accidentally used
these offspring to breed a new generation of lab rats, researchers
discovered that the grandsons of the poisoned rats also produced deformed
sperm.
Skinner’s rats sparked a flurry of new experiments that showed how
methylation could lead to the inheritance of acquired traits. As some
researchers commented, it was as if the work of Jean-Baptiste Lamarck (who
famously posited that the necks of giraffes had lengthened over generations
because they were stretched as the animals reached up to feed) had become
reestablished. Science is rarely so simple—still, epigenetics has Zimmer
wondering whether “poverty, abuse, and other assaults on parents also
impress themselves epigenetically on their children.” The study of
epigenetics is still in its infancy, so it may be years before we know the
answer. With some recent studies showing that epigenetic effects fade over
time, many researchers are unsure whether epigenetics is anything but an
interesting codicil to the conventional genetic theory of inheritance.
The recent development of CRISPR-Cas9 technologies has elucidated yet
another potential pathway of inheritance. Cas9 is an enzyme produced by the
immune systems of bacteria that fights viruses by breaking up their DNA. As
it turns out, it also offers a way to use RNA to guide precise editing of a
genome by removing or adding genetic sequences to chromosomes. CRISPR-Cas9
could be used to edit out defective genes and even insert new ones.
Reporting on CRISPR in 2014, Zimmer realized that he “was witnessing the
beginning of something enormous.” One of the discoverers of the technique,
Jennifer Doudna, was meanwhile having recurring nightmares about her
discovery. In one nightmare she found herself on a beach staring directly
at an oncoming tsunami. In another she met Hitler, who had the face of a
pig. As Doudna spoke, the pig-Hitler jotted down notes.
In one of the first uses of CRISPR-Cas9 for biological control, attempts
are being made to modify mosquitoes so that they cannot carry the malaria
parasite. But because relatively few mosquitoes bear the inserted genes for
malaria resistance, their genetic inheritance is quickly diluted when they
are released into the wild. If the inserted genes are to spread, another
technology known as a gene drive is required. A gene drive is an additional
bit of genetic modification to propagate genes in a population by giving
them a greater than 50 percent chance of being inherited.
As of 2015, results from the mosquito work were mixed, with some female
descendants eliminating the gene that had been inserted into their
ancestor’s genome using CRISPR. But in 2018, after the publication of
Zimmer’s book, researchers announced that they had successfully propagated
genes in mosquitoes using a gene drive. With both CRISPR and gene drive
technologies becoming more powerful by the year, we must look to
visionaries to comprehend its potential. George Church, a geneticist at
Harvard and MIT, believes that CRISPR will inevitably be used to create
genetically “superior” humans. Alterations to our genome will creep in the
door through the treatment of diseases, he says. Imagine if gene editing
can be used to treat wasting muscles, or Alzheimer’s, or to prevent HIV
infection (as was allegedly done to a pair of unborn twins recently in
China)—how long would it be before those same techniques are used to create
super-muscles or super-cognition?
Church is rightly concerned about CRISPR’s potential to permanently alter
human gene lines, as are other scientists. Marcy Darnovsky, the executive
director of the Center for Genetics and Society, thinks it will lead to an
“unregulated marketplace” in which gene editing, which can inflict harm on
unborn children, will run rampant. Given the history of earlier
misunderstandings of inheritance that Zimmer relates, it’s a warning we
better take seriously.
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