in protein evolution, and therefore
macrobiotic speciation, are now well
understood, and closely match the
timescales documented in the fossil
record
5
. The elephant in the room
for many genetic-algorithm opti-
mization processes is therefore that
the number of generations required
for optimization may be high,
whereas the possible throughput
of experiments is often low.
Kreutz et al.
1
have combined solu-
tions to all of the above issues into a
system that holds real promise for
developing useful answers to syn-
thetic problems involving multi-
variate optimizations. The authors
studied the oxidation of methane
(CH
4
) to methanol (CH
3
OH, an
industrially important bulk chemi-
cal) using oxygen gas. This process
is of increasing interest because of
its environmentally friendly creden-
tials; oxygen is readily available from
the atmosphere, and produces no
unpleasant waste products, unlike
many other oxidants. But catalyst
turnover numbers for the reaction (the number
of moles of substrate converted by each mole of
the catalyst before it is inactivated) have been
low, as have the yields in many cases.
The authors therefore designed a droplet-
based microfluidic system that used a genetic
algorithm to optimize the properties of a meth-
ane-oxidation catalyst. The catalyst consisted
of three components, each of which could be
varied. The team began by screening 48 differ-
ent combinations of components for their col-
lective catalytic activity, with every combination
tested in its own droplet. Each combination
consisted of three ‘genes’, sets of compounds
that might act as one of the three components
of the catalyst. The authors identified the best
genes (those that produced the most active
catalysts) and either ‘mutated’ them by chang-
ing a few of their components at random,
or crossed them with other genes. This gen-
erated a new set of 48 genes for a subsequent
round of screening.
Over eight generations of screening, the
team generated an up to sevenfold increase
in the fitness score — a combination of yield
and turnover number — of their catalytic sys-
tem, and also identified the relevant catalytic
components that enhanced fitness. This is an
amazing achievement given the relatively small
number of component combinations (384)
explored. For comparison, there are hundreds
of millions of possible combinations.
The method is also notable because of the
consummate use of the properties of both the
techniques and the materials. The chip mater-
ial chosen by Kreutz et al. was polytetrafluoro-
ethylene (Teflon), a fluorous material in which
all the hydrogens of the hydrocarbon chains have
been replaced with fluorine atoms. Similarly, the
droplets were carried through the microfluidic
microfluidic device. Kreutz et al.
have thus directly addressed — and,
in the case of droplet crosstalk, har-
nessed — the three elephants in the
room associated with microfluidic
devices and genetic algorithms.
This combination of techniques
and materials
1
opens up the possibil-
ity of the evolutionary development
of other, more complex catalysts and
even of artificial enzymes. The appli-
cations are therefore widespread
within biomolecular and chemical
sciences. However, challenges do
remain. Notably, although gases
readily permeate Teflon, liquids do
not. Similarly, the rate of mass trans-
fer through the walls of the droplet-
carrying tubes is limited by the wall’s
permeability, thickness and the
pressure differential across it. These
effects might sometimes combine to
cause a paucity of starting materials,
artificially slowing fast reactions.
Regardless, it will be fascinating to
see what discoveries will be made
as a result of Kreutz and colleagues’
approach. Rarely has a herd of elephants seemed
so productive.
Robert C. R. Wootton is at the School of Pharmacy
and Biomolecular Sciences, Liverpool John
Moores University, Liverpool L3 3AF, UK. Andrew
J. deMello is in the Department of Chemistry,
Imperial College London, London SW7 2AZ, UK.
e-mails: r.c.wootton@ljmu.ac.uk;
a.demello@imperial.ac.uk
1. Kreutz, J. E. et al. J. Am. Chem. Soc. 132, 3128–3132
(2010).
2. Lee, J., Kim, M. J. & Lee, H. H. Langmuir 22, 2090–2095
(2006).
3. Badal, M. Y., Wong, M., Chiem, N., Salimi-Moosavi, H. &
Harrison, D. J. J. Chromatogr. A 947, 277–286 (2002).
4. Huebner, A. et al. Lab Chip 8, 1244–1254 (2008).
5. Hedges, S. B. & Kumar, S. Trends Genet. 19, 200–206 (2003).
device by a fluorous oil. Such fluorous materials
are extremely permeable to gases, particularly
oxygen, so the authors simply perfused the
gaseous starting materials for the reactions
through the walls of the chip (Fig. 1).
Kreutz and colleagues monitored the pro-
duction of methanol in their system using
droplet crosstalk. In this approach, catalyst-
bearing droplets were flanked by droplets
containing colorimetric indicators. These indi-
cators responded to methanol diffusing from
adjacent catalyst-bearing droplets by changing
colour, thus allowing a rapid, on-line assess-
ment of reaction progress. What’s more, the
authors proved that their genetic algorithm
was practically useful in a high-throughput
Figure 1 | Screening catalysts in a microfluidic device. Kreutz et al.
1
have designed a microfluidic system that screens the activity of
catalysts for the oxidation of methane (CH
4
) to methanol (CH
3
OH),
using oxygen as the oxidant. Microdroplets of catalyst solutions are
passed through Teflon tubes by a carrier fluid. The Teflon tubes are
enclosed by stainless-steel tubes, into which pressurized CH
4
and O
2
are
introduced. The gas mixture diffuses through the Teflon tubing and, in
the presence of active catalysts, reacts to produce methanol (CH
3
OH).
At high temperatures, the methanol diffuses through the carrier fluid
to a neighbouring droplet, which contains a colorimetric indicator. The
indicator changes from yellow to purple in the presence of methanol,
with the intensity of the purple colour corresponding to the activity of
the catalyst. (Figure adapted from ref. 1.)
EVOLUTIONARY BIOLOGY
A flourishing of fish forms
Michael Alfaro and Francesco Santini
According to an innovative exercise in ‘morphospace analysis’, modern fish
owe their stunning diversity in part to an ecological cleaning of the slate by
the mass extinction at the end of the Cretaceous.
Fish come in a bewildering diversity of
shapes: trumpetfish, sea horses, pufferfish,
cowfish and anglerfish are just a few exam-
ples. Size, too, varies tremendously in living
species. Some gobies reach less than a centi-
metre as adults, whereas the oarfish stretches
well over 12 metres and the ocean sunfish
can weigh more than a car. These groups,
along with almost two-thirds of all other fish,
belong to a particularly conspicuous section
of the fish tree of life, the spiny-finned fishes
(Acanthomorpha). With 18,000 species, spiny-
fins comprise almost a third of all vertebrates.
Despite, or perhaps because of, this incredible
richness, biologists understand surprisingly
little about the tempo of spiny-fin diver-
sification. As he reports in Proceedings of
the Royal Society, Friedman
1
has searched
for the origins and underlying causes of
shape diversity in spiny-fins across nearly
840
NATURE|Vol 464|8 April 2010 NEWS & VIEWS
© 20 Macmillan Publishers Limited. All rights reserved 10