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biotech and life sciences worldwide as part
of a larger project to map human technologi-
cal development (Fig 1). “Maps can help
answer or at least address a number of key
questions,” said Hoffman. “Where around
the world is biotech really happening or
beginning to happen? How important is eco-
nomic geography now that the life sciences
are spilling out of university, governmental
and industrial laboratories into regional
economies? Where is the search for ‘biotech
gold’ breaking down national boundaries
and political jurisdictions, with different
regions and different countries banding
together to compete in the global economy?”
Indeed, the biotech-clustering craze hasalready created another level of complex-ity: meta-clusters. These are transnational
networks of clusters operating in geographi-
cally connected countries. Europe, in partic-
ular, is a fertile place for such initiatives. The
latest is EuroBioCluster South, which was
announced at the 2005 BioVision conference
held in April 2005 in Lyon, France. The pro-
ject will combine bioclusters from an area
stretching from Heidelberg, Germany, to
Barcelona, Spain, “to stimulate a supra-
regional dynamic of scientific and technolog-
ical growth and international outreach,”
according to an official press release (Grand
Lyon, 2005). The EuroBioCluster’s potential is
expected to exceed that of Seattle, San Diego
and San Francisco combined, and it will have
“the largest concentration of life-science
enterprises in the world, with the presence of
both major groups and start-ups, research
centres, universities and institutions.”
ScanBalt is another main cross-border
effort in biotech and life-sciences develop-
ment, encompassing 11 countries and 85
million people in Northern Europe with 60
universities and 870 biotech-related compa-
nies. “We do not consider ScanBalt to be a
meta-cluster but a meta-region, which is an
important difference,” clarified Peter Frank,
General Secretary of ScanBalt. “Clusters
have a certain dynamic connected to the fact
that activities within a cluster are character-
ized by geographical proximity and a
regional background, while a meta-region
like ScanBalt BioRegion has a different and
complementary dynamic.” A basic role of
ScanBalt is to coordinate between regional
and national networks, promote the estab-
lishment of clusters and increase transpar-
ency and visibility of competencies in the
region, explained Frank.
Although the verdict is still out on the
effectiveness of science parks, incubators
and mega-clusters in boosting local devel-
opment, they will be in fashion for some
time. “Businesses—from high-tech compa-
nies to developers—that get money from
these schemes are happy with their wind-
falls. Politicians are happy to hand out pork
while looking like visionaries,” wrote
Wallsten (2004b). However, “the obsession
with becoming the next biotech hub will
fade in time, just as dotcom dreams did.”
But if a good-practice model prevails for the
establishment of research parks and clus-
ters, if it is based on a thorough evaluation
of local dynamics, research potential and
entrepreneurial environment, and if strict
policies are enforced to select only techno-
logically sound tenants and spin-offs, then
there is space for reasonable optimism that
these investments can spur high-tech and
biotech progress, at least in some cases.
REFERENCES
Critical I (2005) Biotechnology in Europe: 2005
Comparative Study. Lyon, France: BioVision
Cyranoski D (2005) Malaysian biotechnology: the
valley of ghosts. Nature 436: 620–621
DeVol R, Wong P, Ki J, Bedroussian A, Koepp R
(2004) America’s Biotech and Life Science
Clusters: San Diego’s Position and Economic
Contributions. Santa Monica, CA, USA: Milken
Institute
Grand Lyon (2005) EuroBioCluster. Press release,
14 Apr. www.lyon-business.org
House of Commons Trade and Industry Committee
(2003) UK Biotechnology Industry. Twelfth
Report of Session 2002–2003. London, UK:
House of Commons
Imperial College (2005) Spin-out News, 30 Nov.
www.imperialinnovations.co.uk
Jia H, Jayaraman KS, Orellana C (2003) Biotech
parks proliferate, despite concerns over
sustainability. Nat Biotechnol 21: 1259–1260
Ketels CHM (2003) The Development of the
Cluster Concept—Present Experiences and
Further Developments. Düsseldorf, Germany:
Ministry of Economics, Northrine-Westphalia
Porter ME (1990) The Competitive Advantage of
Nations. New York, NY, USA: Free Press
Sansom C (2004) EU expansion: enlarged horizons
or false dawn? Nat Biotechnol 22: 501–504
Stone R (2005) Central Asia. Visions of a biotech
empire on the Kazakh Steppe. Science 308: 1861
The Scripps Research Institute (2005) Scripps
Research breaks ground for construction of
Scripps Florida campus. The Scripps Research
Institute News & Views, 26 Sep
www.scripps.edu/newsandviews/
Wallsten S (2004a) Do science parks generate
regional economic growth? An empirical analysis
of their effects on job growth and venture capital.
Working Paper 04–04. Washington, DC, USA:
AEI-Brookings Joint Center for Regulatory Studies
Wallsten S (2004b) High-tech cluster bombs.
Nature 428: 121–122
Andrea Rinaldi
doi:10.1038/sj.embor.7400633
… the biotech-clustering craze
has already created another level
of complexity: meta-clusters
Ancient DNA research
goes nuclear
A new technique to extract sequence data from nuclear DNA may reveal
exciting new insights into evolution and phylogeny
It is one of the most fascinating questionswe face: how did Homo sapiens—modern humans—evolve? When did
they start using tools, how did they develop
language and why did Homo erectus and
then Homo sapiens thrived while other
human species, such as the Neanderthals,
became extinct? The availability of
advanced genetic technologies, most
notably the polymerase chain reaction
(PCR), originally held great promise to
answer these questions; in theory, sequenc-
ing the DNA from fossils could paint a
picture of the molecular evolution not only
of humans but of other species as well. In
practice most of these expectations have
not been realized, as the analysis of ancient
DNA is anything but easy. The very small
amount of DNA in fossil samples, the decay
of the molecules over time and contamina-
tion with DNA from other organisms have
proven to be considerable hurdles. As a

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©2006 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION EMBO reports VOL 7 | NO 2 | 2006
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result, most knowledge about molecular
evolution comes from the analysis of mito-
chondrial and plastid DNA, simply because
it is more abundant and easier to analyse.
But the analysis of ancient DNA is about
to enter a new era. Two recently developed
techniques—multiplex PCR and a new
genomic sequencing technology—allow
the recovery of meaningful sequence data
from nuclear rather than just mitochondrial
or chloroplast DNA. Many of the field’s
leading researchers are already excited
about the prospects. “I think we will see a
number of studies dealing with functional
genetics, where you take and amplify
sequences, and see phenotypic features
that say something about how the animal
behaved or looked like,” said Eske
Willerslev, from the Department of
Evolutionary Biology at the University of
Copenhagen, Denmark. “We will definitely
see much more in the next two years
because there’s a huge potential out there.”
Although it may never be possible to
recreate extinct organisms from their DNA,
the new multiplexing technique could
enable scientists to expand their study of
phenotypes by investigating properties
such as skin colour or behavioural traits.
Among the many important questions that
could be answered is whether the
Neanderthals—the last human species to
become extinct—were able to speak and,
if so, how well. “To do this, various groups
hope to target the FOX2P gene, which is
believed to confer the ability to speak in
humans,” said Tom Gilbert, an ancient
DNA and evolution researcher at the Niels
Bohr Institute, University of Copenhagen,
Denmark. This could help to resolve the
debate over why the Neanderthals became
extinct around 30,000 years ago, as one
theory claims that modern humans gained
the upper hand linguistically.
Because DNA degrades with timeeven when preserved under idealconditions, sequence amplification
is compromised by deletions or substitu-
tions that either cause the process to fail or
result in mistakes that can lead to false
conclusions. The probability of such errors
is proportional to the length of the strand;
although longer sequences contain more
information, in practice researchers have
had to make do with overlapping shorter
ones, and then painstakingly piece them
together. More importantly, the process is
usually constrained by the small amount of
template DNA in the sample. For this rea-
son, no DNA sequences longer than about
1,000 base pairs (bp) have been recovered,
even from widely studied Pleistocene
mammalian species such as mammoths,
ground sloths and cave bears.
The breakthrough in ancient DNA
sequencing came in 2005, when Michael
Hofreiter from the Max Planck Institute for
Evolutionary Anthropology in Leipzig,
Germany, and colleagues described in
Nature their new multiplexing technique for
reconstructing a longer DNA sequence from
several small molecules (Krause et al, 2005).
They demonstrated this by reconstructing
the entire mitochondrial genome of the
Pleistocene woolly mammoth, Mammuthus
primigenius, comprising 16,770 bp, from
about 200 mg of bone.
In essence, multiplexing is a two-stage
PCR. It uses multiple primer pairs in one
PCR reaction to target subsequences within
the complete DNA sample. In the case of
the woolly mammoth mitochondrial DNA
(mtDNA), 46 such primer pairs were
chosen that marked overlapping DNA
sequence fragments and spanned the entire
mtDNA genome. To cut out the overlaps
and generate coherent products that could
then be amplified in the second PCR stage,
the researchers divided the primer pairs
into two sets, each comprising alternate
pairs. Each of these two sets was amplified
in a multiplex PCR, requiring only as much
ancient DNA template as would be used
normally for a short target sequence.
Having obtained the two amplified
sequences, which together spanned the
whole mtDNA genome, the samples were
divided into 46 parts and used as templates
for a secondary PCR to amplify each of the
46 products separately. Although multi-
plexing does not save time, it allows far
greater scaling up from small samples,
… in theory, sequencing the
DNA from fossils could paint a
picture of the molecular
evolution not only of humans
but of other species as well
Phenotype reconstruction based on mammoth nuDNA (possibly contaminated)
Among the many important
questions that could be answered
is whether the Neanderthals…
were able to speak and, if so,
how well