It Process

NEWS & VIEWS NATURE Vol *** * August ****

level, allowing each dimension to evolve answer this question in Darwin s finches. Such

independently. information would add to the debate over

However, these results do not establish the whether evolution proceeds through the accu-

precise nature of the genetic changes responsi- mulation of many mutations of small effect in

ble for the differences in morphology. Are the many genes, or through one or a few mutations

changes in CaM levels between species due to of large effect in a single gene. Although it is

50 YEARS AGO

one or more differences in the CaM gene itself difficult to generalize from a few examples,

Nuclear magnetic resonance

for example in the flanking regulatory Darwin s finches still have much to tell us about

and electron spin resonance

regions of the genome that control where and the evolutionary process.

It is no new idea that most of the

at what rate the gene is transcribed? Or are Nipam H. Patel is in the Departments of

advances in the techniques of

they due to changes in one or possibly many

chemistry have come from the Molecular and Cell Biology, and Integrative

use of apparatus and methods genes scattered throughout the genome that Biology, and at the Howard Hughes Medical

originally devised by physicists. act upstream of CaM to cause it to be Institute, University of California, Berkeley,

This is particularly true of expressed at higher levels in the developing California 94720-3140, USA.

spectroscopy, where the main beaks of cactus finches? e-mail: *****@******.********.***

applications associated with the Genetic mapping studies in other animals

different frequency bands have 1. Abzhanov, A. et al. Nature 442, 563 567 (2006).

and plants, such as maize (corn) and teosinte

2. Grant, P. R. The Ecology and Evolution of Darwin s Finches

moved over, one after another, (from which maize was domesticated)5, suggest (Princeton Univ. Press, 1999).

from the pure physicist to the that mutations directly affecting the expression 3. Grant, P. R. & Grant, B. R. Science 313, 224 226

chemist It would appear (2006).

level of a single gene have been responsible

4. Abzhanov, A. et al. Science 305, 1462 1465 (2004).

that during the past eighteen for some profound evolutionary changes. 5. Doebley, J., Stec, A. & Hubbard, L. Nature 386, 443 445

months a similar move has The application of mapping techniques could (1997).

been taking place with the

two new techniques of nuclear

magnetic resonance and

electron spin resonance

PARTICLE PHYSICS

As with all techniques which

A finer constant

study the interaction of atoms

with external forces, it soon

became clear that these new

methods also had very great Andrzej Czarnecki

potentialities as tools for

For the first time in a decade, the precision of the fine-structure constant

chemical investigation, and

during the past few years central to understanding the electromagnetic force has improved.

these applications have

But even greater accuracy is required to test new physics.

been brought to light in a very

striking way. D. J. E. Ingram

How does the colour of a rose relate to the precise values came from solid-state systems,

From Nature 4 August 1956.

hardness of oak? To physicists, both result through the discovery of electrical phenomena

100 YEARS AGO from electromagnetism, an interaction whose such as the Josephson and the quantum Hall

Strength of a Beetle Last strength is encoded in one pure number the effects (Fig. 1).

50 & 100 YEARS AGO

night a small beetle (Aphodius fine-structure constant. Appropriately for For the past quarter-century, the world

fossor), the length of which is something introduced at the dawn of quantum record for the most accurate value of has

1/

2 inch, flew in at my window and mechanics, the fine-structure constant is been held by amazing experiments performed

alighted on a table next to me. As denoted by the Greek letter alpha . It was on a single electron trapped in a vacuum per-

it buzzed about I put a lid of a tin meated by electric and magnetic fields3. The

once believed to be a simple fraction, 1/137, a

box over it, but to my surprise the circumstance that provoked theorists to search electron, as a charged and rotating particle, is

beetle walked about bearing the for some deeper meaning to it. Studied closer, a tiny magnet with a strength its magnetic

lid on its back. I then put the tin the denominator turned out not to be an moment given by g (e/2m)s, where e, s

box on top of the lid, and was integer. Writing in Physical Review Letters, and m are the electron s charge, spin and mass.

absolutely amazed to find that Gabrielse and colleagues1 use a measurement The proportionality coefficient g would be 1

the insect tilted up a corner of

of the electron s magnetic moment reported for a classical spinning ball. For the point-like

the combined box and lid, and

in a companion paper2 to find that electron, relativity theory demands that g 2.

nearly escaped. The weight of

1/137.035999710(96), the most accurate This is not yet the whole story. The physical

the beetle when dead was

value yet. But why is this important and vacuum, far from being nothing, vibrates with

1/

2 grain, alive I suppose it was a

why is even this accuracy not enough? activity. Elementary particles borrow energy

little more; but the box and lid

Electromagnetism dominates most phe- from the vacuum to pop up and disappear again

weighed 1758 grains! Assuming

nomena at scales larger than the subatomic through quantum fluctuations. The electron

that the living insect weighed

(which is ruled by nuclear forces) but shorter interacts with such virtual particles, mainly

1 grain, it must have tilted up 1758

than the astronomical (the realm of gravity). photons, and its g-factor is increased slightly by

times its own weight! Of course,

Thus, can be measured in many ways, using an amount that depends on . This deviation,

the strength required to tilt up a

any system of well-understood electromag- known as g minus two ( g 2) is among the

box on edge is nothing like so

netic nature. When Arnold Sommerfeld first most precisely calculated quantities in physics.

great as that required to actually

used in 1915, he named it the fine-structure In fact, quantum electrodynamics, the theory

lift the weight, but nevertheless

constant because it described subtle features of of electron interactions with light, was born

the feat seems to me sufficiently

the radiation spectrum of the hydrogen atom. through efforts to understand its value.

astounding. The dimensions of

the box are 31/8 x 21/8 x 11/2 inches. Its value was initially best determined by mea- The dream of the theorist is an exact expres-

suring atomic transitions. In the 1970s, more sion for g 2 in terms of, but that seems as

From Nature 2 August 1906.

516

2006 Nature Publishing Group

NEWS & VIEWS

NATURE Vol 442 3 August 2006

elusive as deriving itself. For now, only the Could measurements of the electron help

first four terms of the Taylor expansion of g 2 clarify what has or hasn t been seen? To probe

are known (this is a mathematical expression the putative new force the muon might have

Electron g 2 (2006)

consisting of a series of terms that, added sensed, the accuracy of the electron g 2 mea-

together, come closer and closer to the true surements should be improved by a factor of at

Rubidium (2006)

value of a quantity). Getting that far took least a dozen. Of course, an independent value

six decades and spawned a rich tool-box of for would be needed to interpret the result.

mathematical methods and tricks that has Excitingly, atomic studies the original

Quantum Hall

benefited other branches of science. Not least source of information on are currently

effect (2001)

Josephson effect (1998)

among these is the field of symbolic computa- seeing a renaissance, and could produce suffi-

tion, which aims to harness the power and ciently precise values. The new laser-based

1 1 8 10 12

patience of computers to tackle huge algebraic tools of optical lattices and frequency combs,

(1/ 137.035990)/10 6

equations. recognized with the 2005 Nobel Prize in

Physics, have been applied6 to trap rubidium

This theoretical progress has gone hand Figure 1 Approaching alpha. The fine-structure

constant,, is present wherever there is

in hand with experimental breakthroughs. atoms and thus determine with an error of

electromagnetism. The accuracy of its

Whereas particle physicists have consistently seven parts in a billion. This is about nine

determination reflects our degree of

strived to build higher-energy accelerators, times cruder than Gabrielse and colleagues

understanding of various phenomena. Gabrielse

value1. But if the expected improvements in

Gabrielse and Peil at Harvard University

and colleagues value1 using the electron g-factor

succeeded in constructing a cyclotron with the atomic approach materialize, the electron

is the best yet; other sources include photon

the lowest energy so far4. In this cavity, cooled g 2 will be freed to check out new physics.

collisions with rubidium atoms, the Josephson

to 100 millikelvin, a single electron can be Improving our knowledge of the fine-struc-

effect and the quantum Hall effect. Neutrons,

trapped and screened even from some of the ture constant by another order of magnitude

caesium and several other atomic systems have

vacuum fluctuations. Such is the tranquillity of with an independent method is a daunting

also been used.

its setting that individual quantum levels of the task. But the cunning of the hunters justifies

electron motion and spin can be discerned. eventually limit how well can be read off cautious optimism.

Transitions among the lowest-lying states have from g 2. Andrzej Czarnecki is in the Department of

now allowed Gabrielse and colleagues to But this emerging sensitivity to physics Physics, University of Alberta, Edmonton, Alberta

determine the g-factor to an accuracy of one beyond electromagnetism is creating new T6G 2J1, Canada, and the Tri-University Meson

part in a trillion (ref. 2) and, when compared opportunities. The electron has a heavier Facility (TRIUMF), Vancouver, Canada.

with the theoretical expression, improve our cousin, the muon, whose g 2 has recently e-mail: ****@****.********.**

been measured. The result disagrees5 with our

knowledge of (ref. 1).

1. Gabrielse, G., Hanneke, D., Kinoshita, T., Nio, M.

Can the accuracy of be improved indefi- understanding of fundamental interactions by

& Odom, B. Phys. Rev. Lett. 97, 030802 (2006).

nitely? This is unlikely using the electron g 2. a tantalizing 2.8 standard deviations: too much 2. Odom, B., Hanneke, D., D Urso, B. & Gabrielse, G. Phys. Rev.

Gabrielse and colleagues measurement 1 is, to ignore, but not enough to claim a discovery Lett. 97, 030801 (2006).

for the first time, sensitive not only to elec- of something new wiggling in the vacuum. 3. Schwinberg, P. B., Van Dyck, R. S. Jr & Dehmelt, H. G.

Phys. Rev. Lett. 47, 1679 1682 (1981).

tromagnetic forces but also to tiny, strong Nevertheless, this could be the first evidence of

4. Peil, S. & Gabrielse, G. Phys. Rev. Lett. 83, 1287 1290

nuclear effects. This is an impressive achieve- particles that are too massive to have been seen (1999).

ment, but also hints at obstacles ahead: the in our laboratories, but that were perhaps 5. Bennett, G. W. et al. Phys. Rev. Lett. 92, 161802 (2004).

uncertainty inherent in nuclear forces will crucial in the design of the Universe. 6. Clad, P. et al. Phys. Rev. Lett. 96, 033001 (2006).

remarkably promiscuous with respect to

CHEMICAL BIOLOGY

the extein sequences within which they sit.

Cutting out the middle man Indeed, inteins have found widespread appli-

cations in protein engineering as a way to

introduce biochemical and biophysical probes

Tom W. Muir into proteins4.

Protein splicing results in a new polypeptide

Wouldn t it be nice if you could control the function of any protein with one

sequence being produced at the site of intein

small molecule? Unlikely as it sounds, this could become possible through excision. Because a protein s function is inti-

a crafty process known as protein splicing. mately linked to its sequence, splicing has the

potential to regulate the activity of the host

One of the most exciting things about chemi- that could somehow modulate the function of protein. With this in mind, conditional inteins

cal biology is its potential to develop new any desired protein seems impossible. Yet in have been reported whose splicing activity is

the Journal of the American Chemical Society 2, triggered by changes in temperature5 or by the

tools for probing cellular processes. Small

application of small molecules6 8. The appeal

drug-like molecules that can diffuse into Yuen et al. describe the results of a study, based

cells and quickly elicit a discernible response on the pharmacological regulation of pro- of these systems is that inducible inteins can be

offer distinct advantages over genetics-based tein splicing, that suggest this might not be a dropped into target proteins with standard

approaches for exploring the highly choreo- complete pipedream. molecular-biology techniques.

graphed inner workings of a cell1. In particular, The work of Yuen et al.2 builds on a previous

Protein splicing is one of the most dramatic

protein modifications known3. It is a self- study7 from the same group, in which directed

small molecules can allow cellular processes to

be rapidly perturbed in a reversible and often catalysed process in which an internal protein protein evolution was used to develop a con-

tunable fashion, allowing the dynamic features domain, known as an intein, removes itself trollable protein-splicing element that could

to be teased out. But finding a small-molecule from a host protein with concomitant linking be activated by the addition of a ligand

modulator that is specific for one protein is a together of the flanking polypeptides, the a molecule that binds to the protein. The

formidable challenge; finding one molecule exteins (Fig. 1, overleaf). Some inteins are controllable intein was based on a hybrid

517

2006 Nature Publishing Group

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