Labor Day has come and gone, and I am chagrined to find that I haven't
made it through my summer reading. My list comprised only a single
book, but a rather unusual one: the text is three billion years old,
has six billion copies in print, runs three billion letters long (about
one million pages), and is written entirely in four characters (A,
T, C, G) with no spaces or punctuation. The book, of course, is a
great classic, The Sequence of the Human Genome.
Just before the Fourth of July holiday, an international scientific
consortium announced at a White House celebration that it had largely
deciphered the DNA instructions encoded in the human chromosomes.
I felt a special pride in the accomplishment, because my own scientific
group at the Whitehead Institute Center for Genome Research was a
major contributor to the effort.
Now that the hoopla has died down, we've all turned to the work of
preparing a scientific paper to be submitted later this year describing
the findings. The real challenge is ''annotating'' the sequence, attaching
meaning to an otherwise boring string of genetic bits. Aided by computer
programs, we're trying to parse the continuous DNA into distinct genes
and discern each gene's role in making neurotransmitter receptors,
bone proteins, stomach enzymes, reproductive hormones and so on.
We're trying to glean meaning from the breathtaking variations in
the chromosomal landscape, from vast gene deserts to dense urban cores.
And we're trying to reconstruct the glory days of ancient transposable
elements that hopped around our genomes millions of years ago but
have since fallen into ruin.
In effect, we're preparing the first edition of a guidebook, describing
the landmarks of the human chromosomes, designed to shape the experience
of generations of genome travelers to come.
Still, I'm aware that our work is just one of the many ways to breathe
meaning into the human genome. So I was glad to visit the Exit Art
gallery last week in SoHo for the opening of a different kind of genome
annotation project, a show entitled ''Paradise Now: Picturing the
Genetic Revolution'' by 39 artists probing the social meaning of genetics.
The works tackle such themes as genetic identity, species boundaries,
biotechnology, evolution and racism.
Scientific revolutions may start with dry, objective data, but their
ultimate impact depends on human interpretation in a societal context.
Scientific milestones set off a search, often a struggle, for the
metaphors and images that will be used to connect the findings with
our daily lives.
Galileo's discovery in 1610 that Jupiter had moons shook his world's
foundations because it undermined the religious image of an Earth
placed at the center of creation, with all heavenly bodies orbiting
it. After a drawn-out battle, the image came to be replaced by a picture
of humans alone on a small planet circling a mediocre sun in a backwater
of an ordinary galaxy in an unimaginably vast and empty cosmos.
Intriguingly, the Vatican showed that it won't make the same mistake
twice: when scientists in 1996 reported possible evidence for ancient
life on Mars in a meteorite recovered from Antarctica, Roman Catholic
officials swiftly said that such a possibility did not conflict with
religious doctrine but revealed God's greater glory.
Likewise, the struggle over the meaning of the human genome is already
under way. The language and imagery will be important because it will
shape society's choices in the coming decades.
To what extent will we regard ourselves as constrained by our genes?
Brain function, color perception, reaction times, rate of memory formation
and personality are surely affected by slight sequence variations
in genes encoding neurotransmitter receptors and biosynthetic enzymes.
But do these gene sequences define limits that we must live within
or influences that may, if understood, be overcome or turned to an
I already detect a naive biological determinism in some popular writing
on genetics, stretching the science far beyond the data. Human beings
may not be blank slates, but neither is there evidence that the chromosomes
contain the legendary handwriting on the wall.
I'm suspicious of the language of limits. The gene pool has not changed
significantly over the past 5,000 years, but human society and individual
opportunity have been transformed. Moreover, history is littered with
supposedly scientific pronouncements about the limits of women, African-Americans,
Southern Europeans, Asians, Jews. Science has done a singularly poor
job when it has sought to define limits on human potential.
To what extent will we seek to pigeonhole people based on their genes?
Humans are a remarkably homogeneous species, with any two people,
regardless of racial or ethnic group, being 99.9 percent identical
at the genetic level. (By comparison, two random chimpanzees in Africa
show a fourfold greater difference.) Still, the residual 0.1 percent
translates to roughly three million spelling differences, with some
conferring dramatically higher risk of Alzheimer's disease or breast
Will we see genetic variation as an economically efficient way to
divide people based on group or individual risk of disease? Or will
we say, ''There but for the grace of God go I,'' and choose to stand
Will we speak of genetic defects or genetic variants? Clearly, some
DNA changes are unquestionably negative mutations, destroying the
function of a crucial protein. But many of the common ones are likely
to confer mixed blessings-- perhaps an increased risk of infection
by one pathogen, but greater resistance to another. It's easy to slip
into speaking of deviations from an ''ideal'' genotype, although population
genetics instead suggests the image of a genetic tapestry is closer
to the mark.
The hardest question is, To what extent will we decide to reshape
the genes we pass to our children? Some of my close colleagues are
already proposing ways to ''re-engineer'' what they view as an ''imperfect''
human genome--to prevent cancer, slow aging, or enhance memory--by
modifying the human germline. These are serious goals, not to be lightly
dismissed. Yet, I find it unsettling that we've only just skimmed
the three-billion-year-old genetic text and already they're saying,
''Hey! I think I can improve on this!''
Safety is, of course, a major concern. Given the subtleties of human
physiology, quick genetic fixes are likely to do more harm than good.
And the prospect of a ''product recall'' from the human gene pool
is too surreal to contemplate. But there will come a time when we
can do such things safely, and it's not too soon to ask whether we
should. Will we adopt the image of humans as a product of manufacture,
rather than a product of nature? If we cross that fateful threshold,
I don't see how we can ever return.
I part company from some of my colleagues here. While I'm strongly
opposed to laws limiting scientific investigation, I would support
a ban on modifying the human germline. Society could always repeal
the prohibition if we become technically adept enough and morally
wise enough. But we should have to rebut a strong presumption against
Meanwhile, I'm back home in my study sifting through genome analyses
for the scientific paper. I have to explain periodically to my three
wonderful children why Dad is holed up working on the weekend. I try
to give them a sense of what I am laboring over. And, as I do, I find
myself attempting to imagine the new world and new world view that
they will inherit as a consequence of our science. And hoping that
they'll be proud.
Copyright ©2000 by the New York Times Company.
Eric Lander, PhD is the Director, Whitehead Center for Genome Research
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