Saved Wikipedia (June 18, 2022) for "Michael Gruber (author)"

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Michael A Gruber in the U.S., Index to Public Records, 1994-2019

• Name : Michael A Gruber

• Birth Date : Oct 1940

• Residence Date : 1988-2020

• Address : 4523 52nd Ave S / Seattle, Washington, USA / Postal Code: 98118

• Second Address : 1910 Winterport C 1 / Reston, Virginia, USA / Second Postal Code : 20191

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Oct 1 1940 birthdate , listed on passenger/immigration card

Middle name "Alan" / Birthdate Oct 1 1940

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1997 (Oct) Wired Magazine - "Map the Genome, Hack the Genome" by Michael Gruber

Full magazine issue PDF : [HP00BZ][GDrive]

Article below - [HP00C0][GDrive]

MICHAEL GRUBER OCT 1, 1997 12:00 PM

The bright, confident, serious people creating the biotech

industry are the fathers and mothers of something enormous.

They are laying the groundwork for what Bruce Sterling calls,

chillingly, the posthuman. The news that an obscure animal

husbandry lab in Scotland has cloned a sheep – that is,

generated a mammal from a body cell without […]

THE BRIGHT, CONFIDENT, serious people creating the biotech industry

are the fathers and mothers of something enormous. They are laying

the groundwork for what Bruce Sterling calls, chillingly, the

posthuman.

The news that an obscure animal husbandry lab in Scotland has cloned

a sheep - that is, generated a mammal from a body cell without sex -

caused quite a stir, since naturally the first thing everyone thought was,

Now they can clone people. There followed the usual political posturing,

including a ban by President Clinton on federal funding for cloning

people (not exactly a major field), followed by clonist Ian Wilmut's

earnest protestations that all he wanted was a better, more genetically

engineerable sheep, and that he had no intention of cloning people, as

That Would Be Wrong.

But out on the biotech frontier, the news brought mostly shrugs. Out

there, people aren't interested in cloning - a clunky, mechanical matter

to those who dwell among the intimate details of life, down where the

nucleotides and the proteins play. Anyone could have done it. And

besides, where's the payoff? They are not like us, people on the biotech

frontier. But they're not like other kinds of frontierspeople, either.

Look at it this way: every frontier has its own kind of cowboy, but they

are mainly variations on a theme. The itinerant printers who wandered

Europe when movable type was the cutting edge, the iron and steam

masters who made the Industrial Revolution, the people who built and

ran the first railroads, the hot-fist telegraphers, the folks in goggles and

leather jackets who created aviation, the outlaw hackers and the whiz

kids of Silicon Valley - all had, and have, certain essential qualities.

They delight in the mastery of new and powerful skills and the manic

energy this can convey. They're impatient with existing establishments,

with conservative nervousness about the shock of the new. They seek a

limitless El Dorado based on technical wizardry. They speak in their

own cant and despise restraint. Their country is the future - which

today means biotechnology. Biotech will be to the coming century what

electronics has been for the one now passing. Everyone says that. So

where are the cowboys?

This is what I went looking for at the second annual After the Genome

conference, where biotech revolutionists come to show-and-tell,

schmooze, and deal. It's November, and margaritas are flowing by the

bucketful in the lounge of Santa Fe's Bishop's Lodge. Every time you

turn around, a waitress in an off-the-shoulder Mexican blouse places

another half-pint glass of pale green slush in your hand. Amid all the

Southwestern kitsch - saints in mesquite, bowls, baskets, rugs, and

paintings of spiritual Native Americans and sunset landscapes - 80

people are getting mildly stoned and scarfing up guacamole and

canapés.

The drinks and food are free, paid for by the drug companies - the

pharmas. It's like Vegas, except there's more money at stake. Lots more

money. The pharma guys look like everyone else, sweaters and jeans,

everything academic-casual. A little sloppy, but not nerdy, is the desired

effect, except that they stick together in little groups and eye one

another warily. Pharmaceuticals are a US$110 billion-a-year business in

the United States alone, bigger than the software industry - and none of

that is games.

Journalistic ethics prompt me to do some work before I'm too drunk to

stand up, so I go over to conference organizer Roger Brent of Harvard's

med school. You could easily mistake Brent for the character Jeff

Goldblum played in Jurassic Park. The glinting specs and the black garb

are the same, as is the nonstop, mind-boggling monolog. I ask Brent

how he chose the conference title, and he explains that it's a riff on Neil

Young's After the Gold Rush. In other words, the people here are

engaged in what - until we reach other planets - may be the last great

exploitation of a natural resource, and the economics are the same.

Vanderbilt-scale fortunes are going to be built, because, as Brent

explains, there are just so many genes, just as there were just so many

gold mines and railroad routes and furry animals in the early days of the

American West.

The Human Genome Project, a federally funded effort to establish the

DNA sequence and map every gene in the human body - the largest

biology enterprise ever launched - is supposed to be finished early in

the coming century, and it's right on schedule. The human genome (i.e.,

the totality of our genetic information) contains an estimated 100,000

genes. Of these, about 5,000 code for the critical blood-borne proteins

likely to be the prime targets for manipulation by drugs. Once these are

grabbed, there ain't no more.

Grabbed? How can something in every human body on the planet be

owned? Oh, not the gene itself, Brent explains - the gene itself is

nothing but a long string of letters. That's in the public domain, and you

can download it off the Internet. It's what the gene does that's

important, and how to manipulate that - that's the art, and an art can be

patented, in the form of a drug or a technology.

So here is the big problem with the widely heralded Human Genome

Project: just knowing the sequences of all those millions of base pairs -

the building blocks of DNA - does you as much good as knowing where

all the tiny pits are on a compact disc. Without detailed understanding

of how those pits translate into music or software, you don't have a

product. Nearly all the people here are involved in one way or another

in efforts to do just that - to go from tiny pits to music, from code to

salable commodity. And that's why genomics, not plastics, is the word to

whisper in today's graduate's ear.

Circulating through the crowd, I stop at various groups and ask an

unscientific sample of scientists the following question: It's just 100

years since Marconi sent the first radio message and launched an

electronic revolution that has completely transformed the world;

applying that same time frame to biotechnology, what year are we in

now? The consensus is somewhere between 1905 and 1915. I try to

think of a biotechnology as far advanced over what we can do today as

the electronics in the average modern home is over a 1915 crystal radio,

and I decide I don't have quite enough tequila in me for a proper effort. I

also get some strange looks and hesitant answers. The people I talk to

are not enthusiastic about speculation; they're wary of hype; they're

closely focused on the actual, the tools, the little cells. I ask: This is the

frontier, boundless horizons - where do you think we'll be in 2050?

Blank looks. I sense that I don't quite understand what's going on, what

kind of people these are. Not cowboys, that's for sure.

The margarita ladies have vanished, and, sobering fast, we all troop

down to a windowless conference room acting as a lecture hall, 20 rows

of cloth-covered tables and chairs, slide and overhead projectors, a

screen. Over the next three days, we will spend nearly 40 hours in this

room; the amount of time spent talking intensely in small groups is

uncounted, but a lot. Not much of a junket this; the frontiers of science

are a serious place.

The first conference speaker is Craig Venter, president and director of

The Institute for Genetic Research - called TIGR - based in Rockville,

Maryland. Venter, one of the Human Genome Project's prime movers, is

talking about the handful of genomes that already have been

completely sequenced - those for some bacteria and a yeast. Barely 0.2

percent of the human genome has been fully sequenced. That doesn't

sound like much, but the effort has a natural exponential shape - the

more we learn, the easier it is to sequence the remainder.

Venter, a tired-looking, preppily dressed man, clearly has given this talk

before. As he rattles through his spiel, slides popping on the screen

behind him, I realize I am in trouble. Personal disclosure: for various

half-forgotten reasons, I picked up a PhD in biology 25 years ago. In

preparation for this meeting I read an undergraduate genetics text, and

increasingly felt like Rip van Winkle. (Fun facts: Unraveled, the DNA in a

typical cell would be a meter long. All the DNA in an average human

body would reach from Earth to the Sun and back 50 times. This is the

kind of stuff I retain, alas.)

The problem is not concept, but nomenclature. Nomenclature is to

molecular biology as mathematics is to physics - a mind-numbing

barrier for the lay knowledge seeker. There are so many things, in so

many different kinds of cells, and each has its own, usually lengthy,

name. As do the processes by which they interact, as do the techniques

by which those processes are elucidated - all heavily acronymized.

"Upon oligomerization of TNFR-1 by trimeric TNF, TRADD is recruited

to the receptor signaling complex. TRADD can then bind TRAF2, RIP,

and FADD," reads a recent piece in Science. Uh-huh. I scribble notes,

hoping to figure it out later.

By dinnertime the next evening, I'm feeling a lot better, having boned up

on the jargon and prevailed on a substantial number of strangers to give

me minicourses in their life's work. They seem happy to do this; most of

them have a memorized speech communicating the technicalities of

their work in room-temperature terms. I ask Brent about this. Maybe it's

the venture capitalists, he suggests: biotech people are deluged with

offers of funding, and they get good at explaining to nonscientists what

they do. Brent and other academics here get daily cold calls from VCs:

"What're you doing? Anything hot? What do you need?" The financial

market senses something immense growing out there, and despite some

much-publicized failures over the past decade, the money guys are still

flinging their darts, hoping to pop Something Big.

As the presentations roll by in the semidarkness, I fight somnolence

with coffee and begin to discern two big themes. The first is the

industrialization of a set of technologies that had always been a kind of

hand craft, performed by people in the traditional white lab coats - dull,

slow, work growing immense numbers of unicellular organisms and

cutting strands of DNA into tiny pieces, then adding a snip of potentially

interesting DNA or perhaps some gene-modifying chemical and

watching what happens. We heard a lot about automating and

increasing the sensitivity of the assaying gear - the better you can detect

a particular molecule, the less you have to amplify it to make it show up.

Much of biotech depends on the Lego-like qualities of biomolecules - if

you get the surfaces right, they snap together. So you can, for example,

set a trap for a particular protein or nucleotide by labeling a "bait" that

will lock on and show up on a detector.

The other theme is the blossoming romance between biology and the

computer, a jointure called bioinformatics, which is driven by the drug

business's grim regulatory economics. The pharmas will spend a

combined $19 billion this year on R&D. To develop a single drug from a

bright idea to something a doctor can prescribe typically costs between

$360 million and $500 million and takes an average of 15 years.

The journey traditionally begins with the medicinal chemists, who

spend whole careers making one likely organic molecule after another

(at the rate of 100 to 150 a year per chemist). When a potential target is

located - for example, a misbehaving or pathogenic protein - the

molecule cabinet is opened and chemicals that might lock on to the

target's active face are tried out in the lab, one by one, by those folks in

the white coats. The few chemicals that seem to work in vitro (in glass,

in the lab) are then tried out on animals. Such in vivo experiments can

go on for years; the project crashes if the potential drug turns out to be

ineffective or toxic.

For the few drugs that survive, more years of clinical - human - trials

follow. Until the Food and Drug Administration signs off, the pharma

cannot make a dime in the US. And even with an FDA green light, the

pharma still might not make a dime. Only 3 out of 10 drugs ever earn

back their R&D costs. In this environment, any technology that

significantly ups those odds - that speeds drug targeting or improves the

hit rate - is a diamond mine.

A funny kind of frontier, then, dominated by giant pharmas, which are

themselves constrained by a ponderous and ultracautious federal

bureaucracy. The participants here seem to reflect this. They are

cautious, calm, reflective, wary about sharing details of their work. Sure,

we have the Hawaiian shirts, the leather vests, the feathers in hats, the

all-black urban stuff - this is not, after all, a vinyl-siding convention. But

my anarchism meter has not stirred.

On a break I seek out Karen Hopkin, a reporter for The Journal of NIH

Research, and, not incidentally, the creator of Studmuffins of Science, a

calendar featuring pinups of scantily clad, brainy hunks.

Hopkin, arguably the most anarchic person in the room, doesn't think a

biogeek culture exists, mainly because it takes a relatively long time to

get good at biology. There's a lot of respect for people who have been

doing it for a long time, because they are still making contributions. You

don't have these 15-year-olds who know it all. People in biology are

older, they have lives, so your basic prank is lightweight: making

squirters out of dry ice and ethanol, slipping orange juice into urine

samples, things like that. Besides, if you're actually in the process of

turning the world upside down, it may obviate the urge to break into

some Air Force computer and steal a landing-gear repair manual. Ian

Wilmut is easily distinguishable as a personality from Kevin Mitnick or

Steve Jobs. A frontier with no cowboys? I'm missing something.

Maybe it's because biotech is so different. One of the forces that drive

the cowboy or the computer hacker is the sheer addictive power of a

new technology, the sense of total, solo control - 48 hours in front of the

screen, living on Twinkies and Jolt. You don't really get that in biology,

because whatever wonders you accomplish, it's never really solo. In a

very real sense, you always have a partner, life itself - you have to wait

to see what the organism will do. That takes a lot of the thrill out of the

game: you're not in total control.

Moreover, the connection between genetic code and its output is

infinitely more complex and indirect than the analogous connection

between software and what a computer does. And finally, there's the

mystery, the sense of wheels within wheels, of things unseen that you

haven't quite pinned down - a humbling that seems to produce priests

rather than cowboys. Not, of course, that biologists can't be as arrogant

as anyone in science - and this increases, the more molecular and the

less organismic the research. But all in all, training as a biologist tends

to be sobering.

Back at the conference, the session has turned to the peculiar little

software industry growing up around the pharmas. The basic idea of

bioinformatics is simple: instead of laboriously making and testing

hundreds of compounds, you use computer simulation - research "in

silico," as some call it - to zero in on those most likely to work. And

where that leads is what the pharmas call rational drug design. (See

"Rational Drug Design," Wired 5.04, page 80.) From a sequenced gene,

you derive an amino acid chain. The chain provides the relevant protein

and its active sites, which you then use as a sort of template to design

the drug. The big stumbling block is the so-called Folding Problem -

how to go from the code for maybe tens of thousands of amino acids

strung along in a nice neat row to the actual protein's intricate shape

and surface. The standard texts suggest that this is computationally

impossible. (Get 20 different kinds of rubber bands - fat ones, thin ones,

little ones, big ones - tie a couple thousand of them together in a long

string, and stretch them. Now, quick, try to predict the precise shape of

the pile that will result when they snap back together. Hard? Cube that,

and you have something close to the Folding Problem.)

But after dinner the third night, with my margarita level falling

dangerously low, I decide to explore the Folding Problem in the hotel

bar with two people I have selected as the Closest Thing to Cowboys

and the Oddest Conference Couple. Art and Sue Weininger are married

and run a two-person firm called Exonix. They have no physical plant.

Instead, they flit from Silicon Valley to San Francisco to Seattle, using ad

hoc teams at contract labs and cranking out the necessary data and

studies, all of which comes together in their computers.

He's a large, dark, bearded programmer from New York who looks as if

he could be one of the Flying Karamazov Brothers. She's a small straw

blond with pale blue eyes who wouldn't appear out of place posing with

a prize heifer at the Iowa State Fair. They met scuba diving in the

Caribbean, but it is clearly a marriage made in heaven, with major

participation from Wall Street - a literal marriage between computing

and biology. Sue mentions in passing that their firm has product worth

$1.2 billion. I set up another round and put the Folding Problem to her.

She answers with a 10-minute protein lecture of such intensity and

erudition that I feel my face start to tan. The short version is this:

software will be available to solve protein folding by 2000. If she's right,

we will (ultimately) be able to make proteins to order, a technological

advance on the scale of, say, the transistor. No big thing in this crowd.

But it is a big thing, an immense thing, if it works. This is the problem.

The hype that afflicts the software industry is nothing, compared with

biotech's bombast. Everything conceivable in the biologic realm has

been discussed, worried over, science-fictionalized half to death. Of

course, we'll cure all disease, live forever, change our shapes, have

feathers, grow gills and dwell beneath the sea - ho hum, tell me

something I don't know. The hype is like the 19th-century penny

dreadfuls that purported to inform the stay-at-homes about the

Western frontier - it has about as much relation to the reality of today's

biotech people as those tall tales did to some flea-ridden, exhausted

cowhand in 1889 Wyoming.

Maybe a tighter focus will help here. Tom Meade, the only man at the

conference wearing a regular business suit, seems an apt choice - he's

talking about hooking DNA to electronic sensors. Meade is pleasantlooking,

diffident, middle-aged, a Caltech professor who discovered

some years ago that under the right conditions, DNA conducts

electricity: that is, you could shoot electrons down the center of an

intact double helix. Based on this discovery, Meade and a postdoctoral

fellow named Jon Kayyem founded a start-up, Clinical Micro Sensors.

The firm, I discover later when I visit, is housed in a concrete-block

building in the old part of Pasadena, just up the street from a Salvation

Army outpost. Kayyem, a gentle-looking, tall, olive-skinned scion of the

great Lebanese diaspora, gives me the five-minute tour: organic lab, bio

lab, computer room. Biotech is visually unexciting. A time-lapse film of

a cutting-edge operation would show a largely empty room with a good

deal of glassware and silent, boxy machines. At long intervals, a person

in a lab coat walks in and pours vials of colorless liquid into other vials

of colorless liquid. I mention this to Kayyem, who agrees, but adds that

his operation uses metallic compounds, so that some liquids are

colored. The blood races! In the computer room, I meet a couple of

people working with chips, gilded rectangular wafers somewhat smaller

than postage stamps, each sitting in a beaker of, yes, colorless liquid.

What Clinical Micro Sensors does is "solder" a metallic compound to the

end of a single-stranded DNA sequence and connect it to a custommade

computer chip. When finished, each chip has thousands of little

DNA half-chain molecules sticking up from it, waving in a liquid bath

like the fronds of a kelp forest.

The proposed device works on the discovery that electrons travel faster

(technically, impedance is reduced) down a complete double helix than

they do down a single strand. If the sequence used is from, say, the

human immunodeficiency virus that causes AIDS, and your test sample

also contains that sequence, then the sample will mate with the chip

DNA, transforming it into a double helix, and you will see lower

impedance, using the fairly standard electronics to which the chip is

connected. The more viral sequence in the test sample, the lower the

impedance. It now takes weeks to get a viral load reading from a blood

sample sent to a lab; the device Kayyem is working on can produce the

same result in minutes.

This technology would be to medical diagnostics what the ability to

program onscreen instead of batch processing was to software

development. Revolutionary is an abused word in biotech, but here it is

entirely apposite. Are the venture capitalists lining up? Not exactly,

Kayyem says ruefully. The wave has already moved on, and investors

want to know when he will have a handheld version. "The hype element

is so great in this field," Kayyem explains, "that it's interfering with the

development of actual products. As soon as somebody makes an

announcement that they're pursuing something, the field adjusts to

assume that the thing already exists, and they want something even

sexier. It's really strange."

Indeed. And unlike software, a medical product can't just be tossed out

on the market to sink or swim and annoy users with its bugs. The FDA

frowns on this. Here is another reason the cowboy style is suppressed in

biotech: this is serious in a way that most computer stuff simply is not.

This is screwing around with the meat puppet itself, ever a sobering

proposition. I put this thought to Kayyem and ask him about the

apparent absence of biotech mavericks. He went to Caltech, after all,

one of the world's great nerd incubators. What were the differences

between the programmers and the biologists?

"Well for one thing, on the undergraduate level, we had the premeds, so

that most of us were planning to work inside the most conservative

hierarchy there is outside the church." That makes sense. Premeds can

get pretty wild, but there's a limit; the truly weird get culled early.

"The other thing," he continues, reflecting, "is that, unlike the computer

people, we had women."

You mean you had sex?

He laughs. "Oh, no, I mean there were female students, both

undergraduate and graduate, in some fairly high proportion. It makes

for a different social setting."

This also makes sense. On their own, adolescent-type males will get

into shenanigans they wouldn't dream of doing with women around.

Cowboy culture thrives in an all-male setting. (Sociological note: the

biotech gender gap is probably smaller than it is in any other high tech

field. If the gear ever gets cheap enough to allow teenagers to snap

proteins together in the garage, your prototypical gene hacker is as

likely to be a girl as a boy.)

Still, something's missing here, a piece that would explain the odd calm

in the midst of this enormous revolution. We start talking again about

Kayyem's technology. He says he expects to have his first working

prototype in around two years.

"We think it's going to be very important to the AIDS community, the

ability to check viral loadings immediately. A lot of AIDS treatment is

adjusting the mix of drugs, and the amount of virus you have is the best

indication that the treatments are working. Also, there's a lot of selftreatment

that goes on. You read about it on the Net all the time. People

say, Oh, I changed my diet, I did this or that, and I feel much better. Now

they'll be able to tell whether they really are reducing the viral load."

And beyond that?

"Well, you can test for anything, really. You could have a suite of chips

that could test for all sexually transmitted diseases, for example. Or one

for biological contaminants in food. Ultimately, of course, you can do

genetic screening in an office, more or less while you wait."

Gulp. Cheap, quick diagnosis is just one example of what the new

machinery will be able to do. Where is this going to end up? Will

teenage kids indeed be able to mess around with genes in the garage?

Here he's a lot more cautious. "I wouldn't go that far right now. But five

years ago, no one would have said we could 'solder' DNA to a computer

chip. On the market side, there's a definite movement toward people

taking on their own treatment. The AIDS people were the pioneers, but

there's really no limit to what people want to do for themselves -

diabetics, people watching their cholesterol, anyone on a drug regimen."

Kayyem seems to be speculating about as far out as he's comfortable

going, so I don't press him any further. Still, on the plane home it occurs

to me that once you start talking about hooking DNA directly to

electronics, you raise the remote but fascinating possibility of linking

the speed of computers to the gargantuan information-storage and -

processing capacity of living molecules. A 22nd-century technology,

maybe.

But it is while musing about the extreme long term that I come up with

another explanation, maybe the key one, for why the biotech frontier is

not a frontier at all - yet. I had made a scaling mistake, simply because

what's happening now is so very large that it's hard to obtain

perspective. The analogy I began with - the electronic revolution - was

wrong. You don't get a proper frontier until you have a workable

technology in hand, something an ordinary individual can use and

adapt: the printing press, the six-gun, the cheap biplane, the personal

computer. Where we are in biotech is a much earlier stage - it's the age

of exploration, of Plymouth Rock and colonial Williamsburg,

Moctezuma and Cortés. Huge corporate entities are sending out teams

of explorers to claim blank places on the map, where it says "Heere be

dragons." The biotech start-ups are not two guys in a garage like Apple;

they're more like the well-funded caravels of Magellan and Drake,

outriders of competing empires.

Historical analogy is always risky, but let's push this: the 21st century

will be more like the 16th than like the 20th, with biology standing in for

the New World. The pharmas and the big chemical companies are the

great expeditionaries - Cortés, Pizarro, de Soto, Raleigh, and so on.

Government regulatory agencies are - what else? - the European

imperial powers. The pharmas are after treasure, of course. The

regulators want to keep control, which they express as an overarching

social good - back then it was Defense of the Realm and Propagation of

the Faith; today it's Public Health.

Historically, two models emerged: the Spanish and the French ran

tightly controlled mercantile-military operations with no local

autonomy to speak of and a small élite ruling a large, inert mass of

peons. The British, by contrast, chartered looser outfits - gentlemen

adventurers, entrepreneurial land barons, church groups - and stocked

their colonies with criminals, exiled rebels, religious nuts. It was the

offspring of this interesting mix who made the American Revolution and

the frontier society that followed: thousands of ornery rascals lighting

out for the territory, cheap firearms in their hands and their eyes on the

main chance. Pioneers. Mountain men.

But biology? What would it take to transform the clubby little world of

biotech into a true frontier - bursting, incoherent, out-of-control

enterprise, including the garage-based teen gene hacker? First, you'd

need that cheap unit, the biotech Colt Peacemaker or Apple II: push a

button, fiddle with a biochemical, test it, fiddle some more, get

something you can use. We're a long way from that now (although who

knows what long means anymore?). But maybe one day some marriage

between the analytic software dozens of small firms are now pushing

and the kind of machines Jon Kayyem has in his sights will spawn a

truly revolutionary biobox.

The second thing you would need is instant results: the hacker wants

code that does something neat. So what could the biobox do? How

about body modification, for starters? How about untraceable

psychoactive substances, optimized for individuals: Make her fall in love

with you! And if that doesn't work? Fix your brain so you won't care!

The third thing you need is the government either helping (as on the

actual Old West frontier) or on the snooze, as it was when the PC was

being developed. That won't happen anytime soon. The big,

industrialized economies are committed to the Spanish Empire school

of exploration, which means that for the near future, it's going to be a

big boy's game, and the typical player is going to look a lot more like

Hernán Cortés than Daniel Boone. Not a happy thought. Certainly the

feckless cowboy/hacker is far more congenial to the modern way of

thinking than the conquistador, especially since, if the trope is correct,

we're all Aztecs and Shawnee. It's enough to make one look more

benignly on the horrible old FDA as it "stifles private enterprise."

Lest we forget, by the way, the golden age of exploration also included

the biggest uncontrolled biological experiment in human history.

Introduced diseases reduced the New World's indigenous population

some 90 percent. A monster gene-mix party occurred among the

survivors and the newcomers. And there was a worldwide redistribution

of plants and animals that both destroyed or modified whole

ecosystems and provided sustenance for millions who would have

otherwise starved or never been born.

We should not expect the coming century to offer changes any less

dramatic. The world this new age of exploration will usher in, the world

after the genome, will be less like ours than ours is like the Bronze Age.

The bright, confident, serious people of After the Genome 2 are the

fathers and mothers of something enormous, and they are immensely

more scary in their ordered way than the most anarchic cyberpunk

hacker ever born. They are laying the groundwork for what Bruce

Sterling calls, chillingly, the posthuman. I suppose your take on this has

to be intensely personal, depending on what you imagine: a long, long,

long happy lifetime in a Second Eden, or a grim Brave New World under

the thumb of the malign heirs of Squibb and Glaxo.

We can't tell which it will be, any more than the European monarchs

who launched the little ships could predict Chicago. They, too, thought

it was only a gold rush.

The word that keeps flitting through my mind is one that, appropriately

enough, came out of the 16th century. It's the term used in Italy during

the Renaissance to connote the ambiguous feelings roused by mighty

forces beyond the normal human scale: la terribilité. The steel mill

flares, the volcano erupts, the fully armed F-16 shoots into the sky,

Genesis itself cranks up again in the colorless fluid. How horrible, we

say, how marvelous!