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鈥淏EEN THERE, done that, got the T-shirt, seen the movies,鈥� might be the
reaction you鈥檇 expect if you suggested bringing dinosaurs back to life. After
all, Michael Crichton cleaned up on the idea in Jurassic Park. Today,
it鈥檚 almost old-fashioned.

Besides, Crichton鈥檚 naive scientists generated their giant lizards from DNA
fossilised in amber. Most real-life experts argue that DNA is such a fragile
molecule that little if any authentic dino DNA still survives in the world. So
the whole notion of resurrecting dinosaurs is preposterous. Isn鈥檛 it?

Perhaps not. There鈥檚 another source of dino DNA鈥攁lbeit modified by
millions of years of evolution. Modern birds are the closest living relatives of
the dinosaurs. Some would say that taxonomically birds are dinosaurs. So, the
reasoning goes, take some bird DNA, let evolution work on it for the right
amount of time鈥攊n reverse鈥攁nd you could end up with the blueprint
for a dinosaur. Borrow a few tricks from the IVF industry, an egg or two from a
local hen house and you might just hatch a creature from the land before
time.

Still doubtful? Well, a few years ago, plenty of people were. But the success
of a small group of pioneers who have recreated ancient genes and given snakes
back the rudiments of their long-lost legs and hens their teeth, is starting to
convince the sceptics. 鈥淭he technology will be there,鈥� says David Stern, an
evolutionary biologist at Princeton University. 鈥淭hings are happening so rapidly
now.鈥� Just two years ago, Stern predicted that scientists would take two
centuries to resurrect a dinosaur. 鈥淣ow I鈥檇 guess more like 60 to 100 years,鈥� he
says.

The research that might make this resurrection possible stems from the fusion
of two hot new fields: the evolution of development (evo-devo for short) and
comparative genomics. This scientific merger does not have dinosaurs at its
focus, however. The main reason biologists want to rewind evolution is so they
can run it on fast-forward. After all, evolution has been solving problems by
manipulating genes for hundreds of millions of years. Why should today鈥檚 genetic
engineers reinvent the wheel as they try to regrow severed limbs, say, when they
can copy Mother Nature (see 鈥淓volution lends a hand鈥�)?

Up to now, nobody has actually signed up for what might be called the
Jurassic Chicken Project. But it鈥檚 certainly being discussed and the groundwork
has been laid. A small cadre of scientists has begun retrieving long-lost
genomic data. Just as linguists can reconstruct long-lost tongues by looking for
the common roots among modern languages, so geneticists can infer what ancestral
genes must have looked like by comparing the genomes of descendants that have a
common ancestor, says Steven Benner of the University of Florida in Gainesville.
Benner鈥檚 team recently reconstructed a gene that resided in a Cretaceous yeast,
a microbial contemporary of Tyrannosaurus rex, 70 million years ago.

The most treasured skill of modern brewer鈥檚 yeast, Saccharomyces
cerevisiae, is its ability to ferment sugars into alcohol with the help of
the enzyme alcohol dehydrogenase (ADH). Brewer鈥檚 yeast has several versions of
this gene, all derived from a single ancestral copy. Benner鈥檚 team compared them
with ADH sequences from related yeasts, and worked out the sequence of their
common ancestor.

Then they brought the sequence to life using genetic engineering tools to
recreate the gene and produce the ancient enzyme for the first time since
dinosaurs walked the Earth. When they tested its biochemical powers, they found
something surprising. The enzyme was optimised to consume alcohol rather than
create it. Brewer鈥檚 yeast began not as a brewer, but as a lush.

The same approach could be used to derive a dinosaur genome with the help of
modern birds. Comparing the genomes of different birds would yield an ancestral,
dinosaurian genome. Recreate the genome, and the rest is straightforward. Pop a
synthesised T. rex genome, say, into a bird egg of the right size and a
Tyrannosaurus should hatch out.

Of course, reconstructing entire genomes would be vastly more challenging
than single genes. It could involve more than 30,000 genes and millions of
individual changes. Even humans and chimps, who have at least 97 per cent of
their DNA in common, have roughly 90,000,000 differences in their
genome鈥攁nd you might expect many times that number between a chicken and a
dinosaur. But DNA sequencing and computing are advancing at such a pace that a
century from now, it may be possible to crunch the genomes of several key
species on Saturday and finish the genetic analysis on a hand-held computer by
Sunday brunch.

That would get us closer to making a T. rex, but not all the way,
says John Gatesy of the University of California, Riverside. The common ancestor
of modern birds would be a distinctly bird-like creature, not much like the
giant monsters that most capture our imagination. You could try bringing the
next closest relative of dinosaurs, crocodiles, into the comparison, but the
common ancestor of birds and crocs lived about 250 million years
ago鈥攂efore the dinosaurs鈥攕o these kinds of genetic studies will hit
either side of the mark. 鈥淵ou are going to have to make a lot of educated
guesses,鈥� says Gatesy.

Still, salvaging even a few Jurassic genes could yield important insights.
For instance, most experts are convinced that dinosaurs were warm-blooded, but
the issue is still highly contentious. Study the heat tolerance of a few
resurrected enzymes and the issue could be settled once and for all.

In fact, scientists reckon that most of the genes that build a chicken would
be functionally interchangeable with their counterparts in a dinosaur. One of
the revelations of the past decade of developmental biology is the astounding
degree to which the same kinds of gene perform the same function in a wide
variety of organisms. The classic examples are the hox genes, which appeared in
a primitive ancestor of all multicellular life some 700 million years ago. They
establish the general blueprint for the organism鈥檚 structure of head, body,
tail. Organisms as diverse as worms, flies, fish and humans all have versions of
these genes, and they seem to be interchangeable. Move the human gene to a fly,
for example, and it still does the job.

The similarity between genomes probably goes even deeper. Sets of genes often
work together to achieve the same result across a huge variety of species,
implying that these molecular circuits were established very early in evolution.
In all vertebrate limb development, for example, two proteins known as sonic
hedgehog and fibroblast growth factor help promote the growth of the embryonic
limb bud by switching on an array of genes. 鈥淚鈥檝e never seen a triceratops,鈥�
says Cliff Tabin of Harvard University. 鈥淏ut those same molecules built its
濒颈尘产蝉.鈥�

Identifying the developmental genes is probably the easy part, though. Much
tougher will be finding all the various sequences that turn them on and off at
the right times and places in the developing embryo. In theory, you should be
able to reconstruct these regulatory switches in the same way as the genes
themselves. But because regulatory regions are often buried in apparently
non-functional or 鈥渏unk鈥� DNA, biologists have a hard time just finding them, let
alone deciphering their effect.

This could be where the Jurassic Chicken Project hits a brick wall. As we try
to reconstruct dinosaur genomes, there are bound to be important regions where
we simply won鈥檛 know how the genes were regulated. Some regulatory regions
evolve so quickly that they will have been rewritten many times since the
Cretaceous, making it impossible to reconstruct the original. To bridge the
gaps, biologists will need to understand how those genes contribute to every
single tissue in the developing organism, and then construct suitable regulatory
regions from scratch. 鈥淭hat鈥檚 too complex to understand completely, maybe even
in a living animal,鈥� says Jeremy Gibson-Brown of Washington University in St
Louis. Worse still, a given gene can be used for many different purposes during
the development of an organism, posing further headaches for would-be dino
designers. 鈥淔ix gene regulation in one tissue and you run the risk of ruining
another. I don鈥檛 think it is realistic,鈥� says Tabin.

But optimists point out that what may appear to be major differences between
species can sometimes be created or removed with surprising ease. All it takes
is the right molecular signal. In one striking example, Cheng-Ming Chuong of the
University of Southern California in Los Angeles and his colleagues were able to
get the beaks of chicken embryos to grow the buds of teeth, a structure bird
ancestors lost some 60 million years ago (Proceedings of the National
Academy of Sciences, vol 97, p 10,044). All it took to erase the years of
evolution was beads soaked with fibroblast growth factor placed in the embryo鈥檚
mouth. Researchers have partially restored legs to snakes and eyes to eyeless
cave fish with similar ease. 鈥淚n some cases, these ancient circuits are probably
still there,鈥� says Martin Cohn at the University of Reading. 鈥淎ll we need to do
is plug them in.鈥�

Unplugging a circuit added during evolution should be even easier. Feathers,
for instance, are an elaboration of scales, so getting rid of them or halting
them at some earlier stage of development shouldn鈥檛 be very hard, says Chuong,
who also studies feather evolution. Indeed, scientists studying mammalian hox
genes found that inactivating certain hox genes in mice gave them backbones more
akin to those of their ancestors who lived more than 200 million ago (New
Scientist, 28 October 1995, p 30).

So it shouldn鈥檛 be too hard to create a toothy, scaly chicken. And some of
the other changes needed to make a dinosaur may be even easier. In one notable
experiment, biomechanics specialists Matthew Carrano of the State University of
New York at Stony Brook and Andrew Biewener of Harvard University fastened metal
tails onto chicks. They wanted to see whether the redistribution of weight and
torsion would make them stand more upright and result in a thinner, more
dinosaur-like femur.

In one respect, the experiment was a complete failure: instead of standing
tall, the chicks dealt with the weight by crouching even lower. But that did
affect their bones鈥攖hey became even less dinosaur-like (Journal of
Morphology, vol 240, p 237). This suggests to Biewener that posture helps
determine the bone structure. So if scientists can genetically engineer the
chicken hip to give it a more upright posture, it might automatically cause the
rest of the leg to become more dinosaur-like. 鈥淭he body may be doing a lot of
adapting to a few genetic changes,鈥� Biewener says.

If dino engineers do someday manage to turn back the clock, though, even the
most optimistic experts say the best that might emerge from the egg would be a
sort of generic dinosaur. Too many details have been lost along the way to
faithfully recreate a particular species. And soft details such as skin colour
and behaviour, long lost in the fossil record, would essentially have to be
invented. But perhaps with enough tinkering鈥攖o stretch out claws, elongate
necks or increase body size鈥攊t may eventually be possible to create
鈥渄inosaurs鈥� realistic enough for anyone鈥檚 dream or nightmare.

The real barriers to the JCP may in fact be ethical rather than scientific.
If we can revive dinosaurs, why not turn back the clock on human evolution too,
turning a chimp into a facsimile of an australopithecine, say? 鈥淚f something is
possible then someone is going to try it,鈥� says Stern. 鈥淲e have 50 to 100 years
before this happens, and we need that much time to think about the ethical
颈尘辫濒颈肠补迟颈辞苍蝉.鈥�

Other questions will crop up, too. Should we try to atone for centuries of
environmental damage by restoring species that humans have wiped out? What would
be the environmental impact if these animals escaped or were released? Some of
these issues are already being raised by the controversy over genetically
modified food and plans to clone rare or extinct species. The JCP pushes the
boundaries much further.

But because of its practical importance, the revolution in evo-devo and
genomics doesn鈥檛 depend on there being a Tyrannosaurus at the end of
the rainbow. 鈥淟ooking back on the Wright brothers鈥� plane, it was clear there
would be jets someday,鈥� says Rudolph Raff of Indiana University. Right now, he
admits we have only a dim view of what the future holds. 鈥淏ut I think that the
amount of engineering that is possible will match anything in any science
fiction imagination.鈥�

THE melding of evo-devo and comparative genomics offers vast possibilities.
Once we learn how evolution has manipulated the genetic switches that control
development, we may be able to borrow the techniques to redesign livestock and
crops to make much more profound changes than we can achieve with today鈥檚
limited tinkering.

Likewise, medical researchers who know how to elongate a limb, make a head
smaller or alter the shape of a heart may someday use that knowledge to diagnose
and correct birth defects that result when the same genes go awry. And armed
with a deeper understanding of how genes and cells collaborate to create the
parts of the body, doctors will have a better chance of regrowing missing or
damaged limbs, rejuvenating arthritic knees, replumbing clogged arteries, or
coaxing human cells to grow into transplant organs in the lab.

鈥淲e鈥檇 like to learn from the way evolution solved those problems,鈥� says
Cheng-Ming Chuong of the University of Southern California in Los Angeles. 鈥淲e
want to learn how to grow an arm. We know nature learned how over millions of
years of trial and error, so that鈥檚 what we study.鈥� Some evolutionary biologists
go even further. The really interesting questions, they say, lie much further
back in the history of life. Jeremy Gibson-Brown of Washington University in St
Louis and his colleague Ilya Ruvinsky at Harvard University, for instance, are
studying genetic events at the evolutionary branching that led to vertebrates.
They want to answer such basic questions as why vertebrates developed limbs at
all.

The people with the money are starting to take notice. The US National
Science Foundation has begun a special evo-devo programme to fund this type of
work, and universities are beginning to establish new research positions in the
subject. What鈥檚 more, the revolution in genomics is giving the whole field new
tools to work with. Expect evo-devo to become one of the hottest research areas
of the 21st century.