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8/8/2019 Bad seeds, bad science, and fairly black cats
http://slidepdf.com/reader/full/bad-seeds-bad-science-and-fairly-black-cats 1/2
Perspectives
1384 www.thelancet.com Vol 376 October 23, 2010
A couple of weeks ago the press reported, with impressive
unanimity, that “Attention Deficit Hyperactivity Disorder
is genetic”. To the rolling of publicists’ drums (and
geneticists’ eyes) came the news that some children
behave outrageously because they inherit damaged DNA.
The Daily Mail—the UK equivalent of Fox News—came out
with a lengthy and hand-wringing piece entitled “Are
some children just born bad?”, which told dreadful tales
of uncontrollable teenagers and claimed that “previous
thinking was flawed and that some children, through no
fault of the parents, are simply bad seeds”.The behaviour of the media when faced with modern
biology is hyperactive with a deficit of attention to
fact—but geneticists (or their employers) are often to
blame for aggravating the disorder. Journalists are as
addicted to press releases as children are to fizzy drinks
(themselves sometimes claimed to cause its symptoms).
The Wellcome Trust, usually a judicious source of scientific
information, helped fund the research. Its publicity
circular hailed “the first direct evidence that attention-
deficit hyperactivity disorder is a genetic condition”.
With a slurp and a belch the papers swallowed it and the
headlines were born.
Biology is rarely pure and never simple. The Human
Genome Project has turned genetics from a simple
repast based on peas to something more like pea soup.
The public relations people seem not to have noticed.
As a result, and to nobody’s surprise, the scientific paper
itself, published in these august pages, was less confident
about its findings than was the press release (and even
less so than The Daily Mail). The Cardiff University group
found a two-fold greater incidence of “indels”—DNAinsertions and deletions—among a group of 400 or so
such children than in more than 1000 matched controls:
a result that was statistically significant. The discovery
was less simple than it appeared; as the Surrey University
biologist Johnjoe McFadden pointed out, the finding
could be restated to emphasise that most children with
the condition had no detectable inborn abnormality, and
that of every 100 children who inherit such a mutation,
only a few will show signs of the disease.
Most science stories nowadays come from press
releases, a tool once alien to the academic trade but now
rife. Scientists should take warning and should at least
make the effort to read each puff before it enters theblurbosphere. The lessons from the Bad Seed school of
science reporting are stark, manifold, much reiterated,
and widely ignored.
I have never heard the word “breakthrough” uttered
in a laboratory except ironically (of course that could
just be because of the laboratories I have worked in). To
quote Lord Salisbury on the fulminations of 19th-century
publicity seekers, “You should never trust experts. If
you believe the doctors, nothing is wholesome: if you
believe the theologians, nothing is innocent: if you
believe the soldiers, nothing is safe. They all require to
have their strong wine diluted by a very large admixture
of insipid common sense.” False fears are bad enough,but false hopes are even worse and biologists often
generate them.
That B word is sometimes justified. The recent
spectacular success in targeting a somatic mutation borne
by around half of all patients with malignant melanoma
certainly deserves the accolade. But, even there, was it
wise for a certain distinguished biologist publicly to agree
that this was a “a penicillin moment for cancer”? A dose
of insipid common sense—or even a dash of cynicism—
would make for better medicine. The spread of Negative
Chicken Little Syndrome (NCLS), the endless reiteration
of the message that DNA tests, targeted drugs, stem cells,
or gene therapy have stopped the sky from falling is a
The art of medicine
Bad seeds, bad science, and fairly black cats?
G i a n l u c a F a b r i z i o / G e t t y I m a g e s
See Editorial page 1364
See Articles page 1401
8/8/2019 Bad seeds, bad science, and fairly black cats
http://slidepdf.com/reader/full/bad-seeds-bad-science-and-fairly-black-cats 2/2
Perspectives
www.thelancet.com Vol 376 October 23, 2010 1385
Further reading
Bollag G, Hirth P, Tsai J, et al.
Clinical effi cacy of a RAF inhibitor
needs broad target blockade in
BRAF-mutant melanoma.
Nature 2010; 467: 596–99.
Beckers J, Wurst W, Hrabé de
Angelis M. Towards better mouse
models: enhanced genotypes,
systemic phenotyping and
envirotype modelling.
Nat Rev Genet 2009; 10: 371–80.
Schmidt-Kuntzel A, Eizirik E,
O’Brien SJ, et al. Tyrosinase and
tyrosinase related protein 1
alleles specify domestic cat coat
color phenotypes of the albino
and brown loci. J Hered 2005;
96: 289–301.
Youngson NA, Whitelaw E.
Transgenerational epigenetic
effects. Ann Rev Genomics Hum
Genet 2008; 9: 233–57.
Williams NM, Zaharieva I,
Martin A, et al. Rare chromosomal
deletions and duplications in
attention-deficit hyperactivity
disorder: a genome-wide analysis.
Lancet 2010; 376: 1401–09
menace to research, to the reputation of those who do it,
and to the public understanding of what has and has notbeen achieved.
All this makes The Daily Mail headline and its fellows
look pretty murky but the problem is wider and deeper
than that. Geneticists have failed to remind the public
what the word “genetic” actually means. Heritability
implies that gene and environment work, or might be
persuaded to work, together. Why, after all, are taxpayers
spending money on the double helix if there is no hope
of an environmental intervention—a drug, a change in
lifestyle, or cancer surgery after the early diagnosis of a
somatic mutation—to help those at risk from what they
inherit? Everyone in the trade knows this although they
fail to mention it except to their first-year undergraduateclasses. Transcripts of their lectures should be sent out
with every press release.
I often talk to my own beginning undergraduates
about the coat colour mutations of mice. Classics of
Mendelism, they illustrate the elegance and simplicity of
its rules. By the time those students graduate, though,
they have—I hope—been let into the secret of just how
messy the mouse really is, how equivocal is the statement
that a particular gene codes for coat colour, and how the
same mutation may do very different jobs in different
circumstances. In the press release culture, by contrast,
genes do one thing at a time, every quality has its codon,
and all that is inborn is inevitable.Ambiguity about inheritance has a distinguished
history, for Charles Darwin himself noted that blue-
eyed white cats are deaf—that the same inherited
error can have what at first sight seem to be entirely
unrelated effects. Darwin’s cat had an error in a gene
coding for tyrosinase that, when it goes wrong, blocks
the production of melanin. The syndrome is less simple
than it seems. Not only are some albino cats, mice, and
people deaf (the deafness coming from the unmet need
for the enzyme in the brain); but they often have poor
eyesight because of a lack of the melanin that helps to
guide the fibres of the optic nerve during development.
That complicated triple problem can arise from errors inseveral distinct coat-colour genes. They include genes
known as pink-eyed dilution, snowflake, quicksilver , grey
goose, and even Dorian Grey and are scattered across much
of the genome where their structure suggests that they
do baffl ingly diverse jobs.
In addition, many mouse colour changes resemble
human disease genes at the molecular level, although
quite why is often obscure. A certain black mutant is
a pretty accurate model of the nervous degeneration
found in Creutzfeldt-Jakob disease, whereas a yellow
variant that makes its bearers fat might say something
about the inheritance of human obesity. Some mice
with a white spot on the belly tend to develop cataracts,
but others have been used as a model for a rare blood-
platelet disease and yet others for cancer. And why doanimals with a mottled coat tend to accumulate copper,
as in Menkes’ disease? Some of these odd parallels are
understood and some are not, but all point at the dangers
of talking about genes as if they are instruction manuals
for a simple piece of bodily machinery.
As Darwin noticed, cats are more captivating than
mice. I often insinuate them into my lectures, although
the students tend to groan when I mention purrphyria
and phenylkittenuria. A separate mutation within the
tyrosinase locus involves a substitution of a G for an A in
the DNA and the shift of a glycine to an arginine in the
relevant protein. That tiny error gives us the Siamese. It
has an important message for the Bad Seeders.The animal’s pattern, with a black face, nose, ears
and tail (and, if it is a gentleman cat, black testicles) is
certainly genetic and, like the albino mutation, results
from instability in the enzyme. However, the damage
is slight compared to that responsible for true albinism
and as a result the protein works fine in the cold, but
not in the warm. This means that the mutation is
temperature sensitive. The colder parts of the body
(including the testicles, the coolest bits of all) can make
melanin and are black, but the warm body mass lacks the
dark pigment.
Inside every Siamese is a black cat struggling to get
out. If a mutant kitten is kept in a chilly room it will growdark hair; while in a hothouse it will be as white as was
Darwin’s blue-eyed pet. Proud owners have even been
known to shave their favourite’s initial on its flank so
that the bald and cool section goes black and the animal
can strut the streets with pride. For the Siamese, as for
almost everything else, nature and nurture work together
and the cat’s appearance could (in principle at least) be
modified with equal effi ciency either by sophisticated
gene therapy or by the simple twiddle of changing
the thermostat. Indeed, the recent discovery that
mouse mutants can have their looks altered by feeding
their mothers chemicals that alter gene expression
shows just how intricate is the path from helix to haircolour, and opens up the exciting prospect of an anti-
Siamese pill.
The multiply mutated mouse and the black-faced cat are
marvellous examples of how what seems simple is not, of
how nature and nurture work together, and of how little
geneticists understand about their own science. Might
the same, perhaps, even be true for attention deficit
hyperactivity disorder?
Steve JonesDepartment of Genetics, Environment and Evolution, University
College London, London WC1E 6BT, UK