199307
199307
199307
$3.95
July 1993
32
Volume 269
Number 1
42
Viral Quasispecies
Manfred Eigen
The extreme mutability and adaptability of viruses wreaks havoc with the classical notion of species. But where traditional taxonomy has failed, mathematics
may succeed. The author has developed a statistical classication scheme that
provides insights into the evolution of the inuenza virus and the age and origin
of HIV, suggesting new strategies for combating viral diseases, including AIDS.
50
56
68
Scientific American (ISSN 0036-8733), published monthly by Scientific American, Inc., 415 Madison Avenue, New York, N.Y. 10017-1111. Copyright 1993 by Scientific American, Inc. All
rights reserved. No part of this issue may be reproduced by any mechanical, photographic or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval
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76
Fuzzy Logic
COOL
JUST
RIGHT WARM
Too much precision can be a bad thing. An air conditioner that keeps a room at
68 degrees Fahrenheit may make some people uncomfortable. A coeemaker may
produce brew that gives some imbibers the jimjams. But fuzzy programs for camcorders and washing machines enable them to do the job the way you want it done.
84
The discovery that the universe is expanding did for the 20th century what the idea
of the heliocentric solar system did for the Renaissance. Although others contributed to the concept, the athletic Rhodes scholar from Missouri made the construction
of the universe uniquely his own topic and set the agenda of modern cosmology.
90
The vast rain forest cradles a rich, complex community of plants and animals.
Some humans have lived as part of this web of life for thousands of years. But
others, driven by poverty or by entrepreneurial passion, threaten its existence.
Marguerite Holloway traveled widely with scientists who are seeking to reconcile
the need for economic development with preservation of the irreplaceable ecology.
DEPARTMENTS
20
10
Are the Rio initiatives losing momentum? . . . Magnifying astronomers resolution . . . . Supercomputer proof . . . .
Kamikaze satellite . . . . A kinder drug
policy . . . . Regenerating hearing . . . .
PROFILE: Howard Hughes Medical
Institute chairman Irving S. Shapiro.
12
110
Mathematical Recreations
A seamstress grapples with
the topology of garments.
101
Book Review
A historians shortsighted
vision for the 21st century.
120
Page
Source
Page
Source
3233
Nova Press/Sygma
63
3435
64
Boris Starosta
65
Johnny Johnson
6870
Roberto Osti
7273
74
Laurie Grace
77
Michael Crawford
7881
Ian Worpole
85
J. R. Eyerman; LIFE
Magazine, Time Inc.;
courtesy of Henry E.
Huntington Library
4348
49
Jean-Pierre Prvel/
Sygma
5051
52
53
54
55
5657
Peter Trusler;
courtesy of Wildlife in
Gondwana, Reed Books
International (in press)
86
Henry E. Huntington
Library (top), John R.
Hale (bottom right),
Henry E. Huntington
Library (bottom left)
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Abramowicz replies:
Astronomers study rotating stars by
looking at the rotating reference frame.
They consider both the gravitational
and centrifugal forces acting on the stellar material because the introduction of
those ctitious forces makes the problem much easier. My discussion could
have been in terms of free-falling frames
and centripetal forces, but that would
have obscured the subject.
One can tell whether two identical rulers are straight without referring to the
path of light as the standard. The method is used by professional draftsmen:
they simply lay the rulers beside one
another. If the left and right sides of
each ruler match, they are straight. Of
course, the straight rulers will not appear as straight in a curved space!
Perhaps an analogy will explain why
light trajectories are geodesics in fourdimensional space-time but generally
not in three-dimensional space. Each
great circle on a globe is a geodesic line
on the two-dimensional surface, yet, being a circle, it is not a geodesic line in the
three-dimensional Euclidean space in
which the globe rests.
Inspecting Bridges
In Why Americas Bridges Are Crumbling [SCIENTIFIC AMERICAN, March],
Kenneth F. Dunker and Basile G. Rabbat state that The Silver Bridge disaster [at Point Pleasant, W.Va., in 1967]
happened in part because of poor inspection by local authorities. I am surprised to see that statement in Scientific American because there is not the
slightest factual basis for it.
I was closely associated with the investigation of the collapse, beginning in
January 1968 when I identied the fracture in eyebar 330 as the cause. As a
metallurgical study by the National Bureau of Standards showed, the eyebar
had fractured suddenly because of a
stress corrosion crack less than one
eighth of an inch deep that had started
on the surface of the hole in the eye. The
hole was almost completely lled by the
pin that coupled successive links in the
eyebar chain. The end of the pin and the
hole in the eye were also covered by a
plate that prevented visual inspection.
At the time of the collapse of the Point
Pleasant bridge, an identical bridge was
in service a few miles upstream. Natu-
rally, there was great interest in determining whether its eyebars could be inspected. The best brains in the nondestructive inspection eld concluded
unanimously that it could not be done.
Consequently, the bridge was removed.
JOHN A. BENNETT
Bethesda, Md.
Dunker and Rabbat reply:
We thank Bennett for his clarication.
Ironically, lax inspection noted at the
time of the Silver Bridge collapse helped
to trigger a massive federal bridge inspection program, and yet state-of-theart nondestructive testing would not
have detected the hidden defect.
JULY 1893
A very interesting new mammal has
recently been received at the British Museum in the form of a sh-eating rat
from the mountain streams of Central
Peru. The animal is about the size of a
common house rat, but has a attened
head, strong and numerous whisker
bristles, and very small eyes and ears.
The chief interest of the new form centers in the fact of its being wholly a
sh-eater, and in its having in connection therewith its incisor teeth modied
come binding until they have been ratied : 50 nations must approve the climate treaty, 30 the biodiversity treaty.
As of May, only 17 countries had ratied each. And if the pacts take eect
but are not rigorously monitored or enforced, they will become paper tigers,
like the vast majority of international
environmental agreements.
Lack of enforcement could also weaken Agenda 21. Last fall the U.N. set up
a 53-member Commission on Sustainable Development to oversee eorts to
implement the plan. But the commission
has a small sta and no legal power. It
is expected to work much as the U.N.
Commission on Human Rights does, by
using publicity and international opinion to exert moral pressure. There is
no precedent for a group within the U.N.
having the kind of clout that the Commission on Sustainable Development
must have, notes Barbara J. Bramble,
director of international programs at
the National Wildlife Federation. On
the other hand, the U.N. is doing a lot
of unprecedented things.
which provides data and analysis to legislators. The major problem is that we
are almost inured to rhetoric. We have
heard so much about doing these things
without actually doing them.
The UNCED conference, which was
attended by delegates and diplomats
from some 178 countries as well as by
thousands of nongovernmental organizations (NGOs), resulted in the creation
of a seemingly strong global political
will and the endorsement of several important policy documents. Along with
Agenda 21, they include the Rio Declaration (a list of environmental and development concerns that ensures national
sovereignty) and a statement about protecting forests.
In addition, two conventionsone to
prevent climatic change and one to conserve biodiversitywere signed by most
countries. You would still be negotiating these conventions today unless
you had the driving force of UNCED,
Fletcher observes. But following signatures with money and muscle is another
matter. The two conventions do not be-
20
Moonball
Astronomers beat a path
to high resolution
21
plosion the shell stretched to 3.8 thousandths of an arc second (the full moon,
in comparison, is 1,800 arc seconds in
diameter). Observations of Nova Cygnis
spectrum revealed the velocity of the
eeing gas. Combining those data with
the Mark III measurement enabled Eliass group to determine that the nova is
about 9,500 light-years from the earth.
Other ndings from the Mark III have
illuminated the shape and structure of
stars. Stars are so distant in comparison
to their diameters that astronomers have
always considered them as unresolvable
point sources of light. But optical interferometers can resolve the disks of many
stars and reveal features on their surfaces. Michael Shao of the Jet Propulsion Laboratory in Pasadena, Calif., estimates that the Mark III has already resolved about 200 stellar disks.
One surprising result of observations
done on the Mark III and elsewhere is the
discovery that stars are not round, says
Richard S. Simon of the Naval Research
Laboratory. Many red giant stars, including the bright star Betelgeuse and the
well-known variable star Mira, exhibit peculiar egglike shapes, presumably because of the huge convection currents
Banzai!
enerally, old satellites dont die; they just fade away.
Yet there are exceptions. This past spring the Japanese Institute of Space and Astronautical Science
( ISAS) decided to send its Hitin satellite into oblivion not
with a whimper but a bang. Rather than flinging the aging
spacecraft into the nether reaches of the galaxy, ISAS piloted it straight into the moon. On April 10, when the 315pound probe crashed at roughly 5,600 miles per hour, it
exploded in a bright flash, throwing up dust and digging
out a crater that astronomers hope will serve as a new
benchmark for planetary science.
Hakan
Svedhem, a physicist with the European Space
Agency, heard rumors of ISASs plans two weeks before
the execution date and scrambled to persuade astronomers to train their telescopes on the moon that night. It
was a great opportunity to observe from the ground a really giant impact as it happens. This has not been done before, Svedhem says.
Three observatories around the world signed on. But as
the kamikaze satellite plunged toward its fiery demise,
the telescope in Irkutsk was jammed up with technical difficulties, and another in Indonesia was rained out. The last
hope was David Allen, an astronomer at the Anglo-Australian Observatory who has a reputation for making difficult observations. If anybody could get this shot, David
could, says Alistair Glasse of the Royal Observatory in Edinburgh. But because of miscommunication about the time
of impact, Allen was unwittingly running behind schedule.
Just seconds before the collision, Allen got the cameras
rolling on the observatorys infrared imaging spectrometer
and recorded half a dozen frames as the flash lit up the lu-
22
nar night. The intensity of the burst and the apparent lack
of a sizable dust cloud make Glasse suspect that Hitin hit
solid rock, converting nearly all its kinetic energy to heat
and light. Svedhem points out, however, that because
ground zero lay about 10 kilometers within the Cimmerian side of the terminator between night and day, a large
dust cloud could easily have been cloaked in darkness.
The deceased was born Muses-A, a small craft designed
to help Japanese astronavigators hone their lunar swingby skills in preparation for a joint mission with the National Aeronautics and Space Administration. Christened Hitin
(a goddess of music) after its launch on January 24, 1990,
the satellite surpassed its one-year life expectancy and after a second year in high earth orbit was sent to wheel
round the moon. While it was en route, Svedhem used the
instrument to collect data on cosmic dust.
Hitins grand finale was not intended to benefit science.
ISAS officials gave only vague explanations for their decisionsomething about leaving fragments for their greatgrandchildren to find, Svedhem reports. But the satellite
may yet attain martyrdom by providing a rare controlled
experiment for planetary scientists. The correlation between the size and velocity of a meteorite and the size of the
crater it creates is based on theoretical calculations and has
never been verified by observations, Svedhem explains. In
this case, we had a very well defined mass and velocity. But
of course we cannot see the crater yet; it is quite small.
Svedhem hopes Hitins successor will pay a visit to the
grave site and send back images of the crater. Meanwhile
he and Glasse will glean all they can from their pictures of
the day the Muses died.
W. Wayt Gibbs
tice points shrinks to zero and the number of lattice points increases to innity. In these limits, one should be able to
come up with observable quantities. Indeed, researchers have used lattice QCD
to explain quark connement, which accounts for why no one can see any free
quarks: it would take an innite amount
of energy to isolate a quark.
Coming up with the masses of hadrons has proved even more elusive. The
calculations require that you look at
all possible dierent congurations of
quarks, antiquarks and the chromoelectric eld on the lattice, says Donald H.
Weingarten, who headed the IBM team.
For meaningful results, large lattices are
necessary, and that entails more involved
calculationsmore than 100 million billion arithmetic operations.
Hence the need for a supercomputer.
Weingarten and his IBM colleagues Frank
Butler, Hong Chen, Jim Sexton and Alessandro Vaccarino turned to GF-11, a
massively parallel computer they helped
to develop for QCD calculations. The
A supercomputer backs
the theory of quarks
23
A Kinder War
Harm reduction gains ground
as an approach to drug abuse
Reno urged that nonviolent drug offenders be handled with a carrot and
stick approach, in which they can avoid
prison by submitting to a treatment program and staying o drugs; urine tests
would ensure compliance. Such a plan
has been carried out in Dade County during the past four yearswith great success, Reno said. This system has also
been favored by Lee P. Brown, former
commissioner of police in New York
City, whom Clinton named head of the
Oce of National Drug Control Policy.
Some prominent jurists have proposed more radical measures. One is
Whitman Knapp, a senior federal judge
in New York State (famed for having
led a commission that investigated police corruption in New York City two
decades ago). Earlier this year Knapp
announced he would refuse to consider
drug cases subject to mandatory sentencing laws. He subsequently argued
that Congress should repeal all federal
laws banning drug sales or possession
and permit states to devise alternatives
to prohibition.
Opponents of such wholesale decriminalization fear any benets would be
oset by a tremendous upswing in the
abuse of drugs such as cocaine and
heroin. David F. Musto, a historian at
Yale University, suggests in the 1987
book Dealing with Drugs that in 1900,
before opioids were prohibited in the
U.S., the rate of opioid addiction was at
a level never equaled or exceeded.
Trebach challenges this claim. He argues that estimates of the number of
addicts varied wildly at the turn of the
century, as do current estimates; the historical evidence can be used to buttress
any conclusion. The charge that prohi-
Healing Hearing
Regrowing damaged ear cells
might eventually cure deafness
BILLIONS OF DOLLARS
1988
1989
1990
YEAR
1991
1992
110
11
100
10
90
80
I.V. DRUG USERS CONTRACTING AIDS (ANNUAL)
70
1988
1989
1990
1991
1992
SOURCES: Centers for Disease Control (red line), Drug Abuse Warning Network (blue line)
26
8
7
LAURIE GRACE
THOUSANDS
THOUSANDS
120
EAR CELLS CAN REGENERATE under some conditions, according to Thomas R. Van
De Water (left) and Hinrich Staecker ( right) of Albert Einstein College of Medicine.
27
JOHN MCGRAIL
28
Cooperation between
business and the
government has
slipped a little bit.
fair amount of intellectual discipline to
recognize that R&D is essential to prepare a company for ones successors,
he reects. Any CEO who is not thinking long-term is tempted to cut.
During the same period, he became
an outspoken champion of corporate
social responsibility as a founder of
the Business Roundtable in 1972. The
roundtable still exists as an association of business executives that, according to its literature, develops positions
which seek to reect sound economic
and social principles. Shapiro tried, he
says, to create the feeling that you have
to be a constructive citizen whatever
your private political beliefs.
He believes the eorts have had an
enduring inuence, especially easing
the almost open warfare in the 1970s
between business and an absolutist
Environmental Protection Agency. But
Shapiro sees troubling signs of deterioration in that entente cordiale. The Business Roundtable, he notes, is less closely identied with government-business
cooperation than it was: It has slipped
a little bit, he says.
Shapiros message secured him a position on a government advisory committee during the Carter years. There
was a price to payduring the Reagan
terms, he says, he was twice approached
about working for the executive branch,
once to consult on defense reforms and
once as an adviser on Middle East politics. But his ties with the Carter administration apparently proved too much
for the White House. Even though years
earlier he had taken his friend George
Schultz on a tour of Israel and Jordan
(which Shapiro says gave the future
secretary of state his education about
the region), the job oers mysteriously
evaporated. They blackballed me, he
states matter-of-factly.
His talent was nonetheless sought by
the legal profession. After retiring from
Du Pont, he promptly took a partnership in the Wilmington oce of Skadden, Arps, Slate, Meagher and Flom, a
powerhouse law rm with oces in 12
countries. Then, in 1984, he became one
of eight prominent citizens appointed
by a Delaware judge as trustees to restore the Howard Hughes Medical Institutes aairs to order. Shapiro threw
himself into rebuilding relations with
ocialdom. The rst thing we tried to
do was end the running sore with the
IRSthat was enough to turn your hair
white, he grimaces.
Shapiro still retains links with Du
Pont and displays his enthusiasm for
industrial research on a wall of his law
oce overlooking the Delaware River.
Behind his desk hangs a copy of a painting of the three Du Pont cousins, greatgrandchildren of the companys founder,
Eleuthre Irne du Pont de Nemours,
who bought the company in 1902 and
turned it into a world leader. These days
Shapiro says he is encouraged by the
Clinton administrations stated intention of implementing a vigorous technology policy. Industry has sometimes
not taken research seriously enough, he
muses. The government might make
mistakes, but I know we also made mistakes when I was at Du Pont.
Shapiro now spends four days a week
at Skadden, Arps and one day a week
on Hughes business. But he makes a
point of going to the institutes scientic briengs, even though he does not
follow many of the reports. I go to put
names and faces together, he explains.
Theres a great value in letting scientists know who I am. When a researcher wrote him recently to take exception
to a Hughes policy on intellectual property, I called her up and said, Lets get
together and talk, he says. You can
do a lot, assuming good faith.
Indeed, the institute has initiated
a grants program to fund investigators in countries such as Mexico, Canada, New Zealand, Australia and Britain.
Shapiro also sees a great opportunity
beckoning in Eastern Europe and the
former Soviet Union, where $10,000
will buy you a lot of science. Plans for
an initiative in those regions are well
advanced.
Impatiently acknowledging a few
of societys more crushing problems,
Shapiro nonetheless predicts that the
U.S. in the next century will be historys richest society in quality of life.
He nds his personal reward when
he reads a popular account of some
biomedical discovery and realizes one
of our people has really moved the
ball forward, and its because we supplied the money and picked the right
person.
Tim Beardsley
SCIENTIFIC AMERICAN July 1993
29
Risk Analysis
and Management
Inadequate approaches to handling risks
may result in bad policy. Fortunately,
rational techniques for assessment now exist
by M. Granger Morgan
mericans live longer and healthier lives today than at any time in
their history. Yet they seem preoccupied with risks to health, safety and
the environment. Many advocates, such
as industry representatives promoting
unpopular technology or Environmental
Protection Agency staers defending its
regulatory agenda, argue that the public
has a bad sense of perspective. Americans, they say, demand that enormous
eorts be directed at small but scarysounding risks while virtually ignoring
larger, more commonplace ones.
Other evidence, however, suggests that
citizens are eminently sensible about
risks they face. Recent decades have witnessed precipitous drops in the rate and
social acceptability of smoking, widespread shifts toward low-fat, high-ber
diets, dramatic improvements in automobile safety and the passage of mandatory seat belt lawsall steps that re-
32
evaluating dangers to the general welfare; they will also have to adopt new
communication styles and learn from
the populace rather than simply trying
to force information on it.
EFFECTS PROCESSES
EXPOSURE PROCESSES
RED SUNSETS
SULFUR COMPOUNDS
CHEAP
ELECTRICITY
ACID RAIN
RESPIRATORY
PROBLEMS
INCREASED
PLANT YIELDS
(left ). After the results of exposure have been quantified (second panel ), they must then be ltered through public perceptions, which cause people to respond more strongly to some
only estimate the probability that individual elements will fail to nd the
chance that the entire system will cease
to function under a particular set of
circumstances. Norman C. Rasmussen
of the Massachusetts Institute of Technology was among the rst to use the
method on a large scale when he directed a study of nuclear reactor safety in
1975. Although specic details of his estimates were disputed, fault trees are
now used routinely in the nuclear industry and other elds.
Boeing applies fault-tree analysis to
the design of large aircraft. Company engineers have identied and remedied a
number of potential problems, such as
vulnerabilities caused by routing multiple control lines through the same area.
Alcoa workers recently used fault trees
to examine the safety of their large furnaces. On the basis of their ndings, the
company revised its safety standards to
mandate the use of programmable logic
controllers for safety-critical controls.
34
PERCEPTION PROCESSES
VALUATION PROCESSES
ACID RAIN
RED SUNSETS
CHEAP
ELECTRICITY
INCREASED
PLANT
YIELDS
RESPIRATORY
PROBLEMS
aspects of risk than to others. Ultimately, costs and benets will be weighed. Agreeing on the values used to make decisions and making sure that all relevant eects
are taken into account are crucial , but often neglected, parts of the process.
fter they have determined the likelihood that a system could expose
people to harm and described
the particulars of the damage that could
result from exposure, some risk analysts
believe their job is almost done. In fact,
they have just completed the preliminaries. Once a risk has been identied
and analyzed, psychological and social
processes of perception and valuation
come into play. How people view and
evaluate particular risks determines
which of the many changes that may
occur in the world they choose to notice and perhaps do something about.
Someone must then establish the rules
for weighing risks, for deciding if the
risk is to be controlled and, if so, how.
Risk management thus tends to force a
society to consider what it cares about
and who should bear the burden of living with or mitigating a problem once
it has been identied.
For many years, most economists and
technologists perceived risk simply in
terms of expected value. Working for
a few hours in a coal mine, eating peanut butter sandwiches every day for a
month, and living next to a nuclear power plant for ve years all involve an increased risk of death of about one in a
million, so analysts viewed them all as
equally risky. When people are asked
to rank various activities and technologies in terms of risk, however, they produce lists whose order does not correspond very closely to the number of expected deaths. As a result, some early
risk analysts decided that people were
confused and that their opinions should
be discounted.
Since then, social scientists have conducted extensive studies of public risk
perception and discovered that the situation is considerably more subtle. When
people are asked to order well-known
hazards in terms of the number of
deaths and injuries they cause every
year, on average they can do it pretty
well. If, however, they are asked to rank
those hazards in terms of risk, they produce quite a dierent order.
People do not dene risk solely as the
expected number of deaths or injuries
per unit time. Experimental psychologists Baruch Fischho of Carnegie Mellon
University and Paul Slovic and Sarah Lichtenstein of Decision Research in Eugene,
Ore., have shown that people also rank
risks based on how well the process in
35
sured on the same scale. When the absolute magnitude of net benets cannot be estimated, however, rules based
on relative criteria such as cost-eectiveness can still aid decision makers.
Rights-based rules replace the notion
of utility with one of justice. In most
utility-based systems, anything can be
subject to trade-os; in rights-based
ones, however, there are certain things
that one party cannot do to another
without its consent, regardless of costs
or benets. This is the approach that
Congress has taken (at least formally)
in the Clean Air Act of 1970: the law
does not call for maximizing net social
benet; instead it just requires controlling pollutant concentrations so as to
protect the most sensitive populations
exposed to them. The underlying pre-
ncertainty is a central element of most problems in- the results are to the dollar values placed on life or health.)
volving risk. Analysts today have a number of softNet social costs, in this model, are simply the sum of
ware tools that incorporate the effects of uncertainty. These control costs and mortality. At $300,000 per death averttools can show the logical consequences of a particular set ed, their most likely value reaches a minimum when TXC
of risk assumptions and rules for making decisions about emissions are reduced by 55 percent. At $3 million, the
it. One such system is Demos, developed by Max Henrion optimum reduction is about 88 percent.
of Lumina Decision Systems
Demos can also calculate a
TXC
in Palo Alto, Calif.
form of correlation between
BASE CONCENTRATION
To see how the process
each of the input variables
works, consider a hypothetiand total costs. Strong correEMISSIONS
HEALTH DAMAGE COEFF
CONCENTRATION
THRESHOLD
cal chemical pollutant, TXC.
lations indicate variables that
REDUCTION
To simplify matters, assume
contribute significantly to the
CONTROL COST COEFF
HEALTH DAMAGE
that the entire population at
uncertainty in the final cost
POPULATION
risk (30 million people) is exestimate. At low levels of polposed to the same dose
lution control, possible variaEXCESS DEATHS
VALUE OF A LIFE
CONTROL COSTS
this makes a model of expotions in the slope of the damsure processes unnecessary.
age function, in the location
The next step is to construct
of the threshold and in the
TOTAL COST
EXPERT EVALUATION
a function that describes the
base concentration of the polrisk associated with any givlutant contribute the most to
UNCERTAINTY
en exposure levelfor examtotal uncertainty. At very high
ANALYSIS
ple, a linear dose-response
levels of control, in contrast,
function, possibly with a BLOCKS in the diagram above can be expanded to call
almost all the uncertainty dethreshold below which there up a window containing graphs and tables for their asrives from unknowns in the
is no danger.
cost of controlling emissions.
sumptions, equations and probability distributions.
Given this information, DeFinally, Demos can commos can estimate the number of excess deaths caused pute the difference in expected cost between the optimal
every year by TXC exposure. According to the resulting cu- decision based on current information and that given permulative probability distribution, there is about a 30 per- fect informationthat is, the benefit of removing all uncercent chance that no one dies, about a 50 percent chance tainties from the calculations. This is known in decision
that fewer than 100 people die each year and about a 10 analysis as the expected value of perfect information; it is
percent chance that more than 1,000 die.
an upper bound on the value of research. If averting a sinMeanwhile, for a price, pollution controls can reduce gle death is worth $300,000 to society, this value is $38
the concentration of TXC. (The cost of achieving any giv- million a year; if averting a death is worth $3 million, it is
en reduction, like the danger of exposure, is determined $71 million a year.
by consultation with experts.) To choose a level of polluAlthough tools such as Demos put quantitative risk analtion control that minimizes total social costs, one must ysis within reach of any group with a personal computer,
first decide how much society is willing to invest to pre- using them properly requires substantial education. My colvent mortality. The upper and lower bounds in this exam- leagues and I found that a group of first-year engineering
ple are $300,000 and $3 million per death averted. (Pick- doctoral students first exposed to Demos tended to ignore
ing such numbers is a value judgment; in practice, a cru- possible correlations among variables, thus seriously overcial part of the analysis would be to find out how sensitive estimating the uncertainty of their results.
38
tributor to holes in the ozone layer. (Willett Kempton of the University of Delaware has found very similar perceptions.)
NOT OBSERVABLE
UNKNOWN TO THOSE EXPOSED,
EFFECT DELAYED, NEW RISK,
RISKS UNKNOWN TO SCIENCE
DNA TECHNOLOGY
MICROWAVE OVENS
ELECTRIC FIELDS
WATER FLUORIDATION
SACCHARIN
WATER CHLORINATION
ORAL CONTRACEPTIVES
VALIUM
CONTROLLABLE
NOT DREAD, NOT GLOBAL
CATASTROPHIC, CONSEQUENCES
NOT FATAL, EQUITABLE, LOW
RISK TO FUTURE GENERATIONS,
EASILY REDUCED, RISK
DECREASING, VOLUNTARY
NITRITES
POLYVINYL
CHLORIDE
DIAGNOSTIC
X-RAYS
IUDS
ANTIBIOTICS
LEAD (AUTOS)
LEAD PAINT
ASPIRIN
DES
NITROGEN FERTILIZERS
RADIOACTIVE WASTE
NUCLEAR REACTOR ACCIDENTS
PESTICIDES
URANIUM MINING
ASBESTOS
PCBS
NUCLEAR WEAPONS
INSULATION
FALLOUT
SATELLITE CRASHES
MERCURY
COAL-BURNING POLLUTION
VACCINES
SKATEBOARDS
POWER
MOWERS
SMOKING (DISEASE)
SNOWMOBILES
TRAMPOLINES
CARBON MONOXIDE
(AUTOS)
BLACK LUNG
STORAGE
AND TRANSPORT
OF LIQUEFIED
NATURAL GAS
LARGE DAMS
SKYSCRAPER FIRES
TRACTORS
CHAIN SAWS
HOME SWIMMING
POOLS
UNCONTROLLABLE
DREAD, GLOBAL CATASTROPHIC,
CONSEQUENCES FATAL, NOT
EQUITABLE, HIGH RISK TO
NERVE GAS FUTURE GENERATIONS, NOT
ACCIDENTS EASILY REDUCED, RISK
INCREASING, INVOLUNTARY
UNDERWATER CONSTRUCTION
COAL-MINING ACCIDENTS
SPORT PARACHUTES
ELEVATORS
DOWNHILL SKIING
GENERAL AVIATION
HIGH CONSTRUCTION
RAILROAD COLLISIONS
COMMERCIAL AVIATION
RECREATIONAL BOATING
MOTORCYCLES
BICYCLES
ALCOHOL-RELATED ACCIDENTS
FIREWORKS
AUTO RACING
AUTO ACCIDENTS
HANDGUNS
DYNAMITE
OBSERVABLE
KNOWN TO THOSE EXPOSED,
EFFECT IMMEDIATE, OLD RISK,
RISKS KNOWN TO SCIENCE
Risks in the upper right quadrant of this space are most likely to provoke calls for government regulation.
FURTHER READING
RATIONAL CHOICE IN AN UNCERTAIN
WORLD. Robyn M. Dawes. Harcourt
Brace Jovanovich, 1988.
READINGS IN RISK. Edited by Theodore S.
Glickman and Michael Gough. Resources for the Future, 1990.
UNCERTAINTY: A GUIDE TO DEALING
WITH UNCERTAINTY IN QUANTITATIVE
RISK AND POLICY ANALYSIS. M. Granger
Morgan and Max Henrion. Cambridge
University Press, 1990.
COMMUNICATING RISK TO THE PUBLIC.
M. Granger Morgan, Baruch Fischho,
Ann Bostrom, Lester Lave and Cynthia
J. Atman in Environmental Science and
Technology, Vol. 26, No. 11, pages 2048
2056; November 1992.
RISK ANALYSIS. Publication of the Society for Risk Analysis, published quarterly by Plenum Publishing.
41
Viral Quasispecies
The standard definition of a biological species does not apply
to viruses. A more expansive and dynamic view of viral
populations holds clues to understanding and defeating them
by Manfred Eigen
42
species is not merely semantic. It offers insights into the behavior of viruses.
In the case of AIDS, for example, it helps
in determining when the human immunodeciency virus ( HIV ) rst evolved
and where it may have come from. If
one were to extrapolate only from the
epidemiologic data, AIDS would seem to
have rst appeared in 1979. Our data, in
contrast, suggest that HIV is a very old
virus. Moreover, the quasispecies concept points toward potential treatments
for AIDS and other diseases that have
so far been resistant to vaccines.
plementary plus strands before viral replication can begin. Inuenza A, one of
the most common epidemic diseases,
is caused by a minus strand virus.
A third class of single-strand RNA
viruses consists of retroviruses. After a
retrovirus infects a host cell, a viral enzyme called reverse transcriptase changes the single strand of viral RNA into a
double strand of deoxyribonucleic acid
(DNA). That DNA can then incorporate
itself into the hosts genome, thereby
making the viral message an inheritable feature of the cell. HIV belongs to
the retroviral family. Its target is the immune system, which ought to provide
protection against the virus.
Because viruses are so dependent on
the replicative systems of their hosts,
scientists generally believe viruses in
their present form must have evolved
after cellular life. It is even possible that
viruses descended from parts of their
hosts genetic programs that turned
their inside knowledge of cells to the
goal of duplicating themselves. Whatever the case, viruses are useful models
for studying how molecules may have
organized themselves into self-perpetuating units at the dawn of life. They
show how information can be generated and processed at the molecular level. The essence of their genetic information is self-preservation, which they
achieve through mutagenesis, reproduction, proliferation and adaptation to a
steadily changing environment.
The genome of a single-strand RNA
virus such as HIV, which comprises only
10,000 nucleotides, is small and simple
compared with that of most cells. Yet
from a molecular standpoint, it is unimaginably complex. Each of those nucleotides contains one of four possible
bases: adenine, uracil, guanine or cytosine. The unique sequence specied by
the genome of HIV therefore represents
just one choice out of 410,000 possibilitiesa number roughly equivalent to a
one followed by 6,000 zeros.
Most such sequences would not qualify as viruses: they could not direct
RETROVIRUS
PLUS STRAND
RNA VIRUSES
LEVIVIRUS
(PATHOGEN OF
BACTERIA)
HUMAN IMMUNODEFICIENCY VIRUS
(CAUSES AIDS)
TOBACCO MOSAIC VIRUS
(PATHOGEN OF PLANTS)
PICORNAVIRUS (CAUSES
POLIO AND OTHER
DISEASES IN ANIMALS)
DOUBLE-STRAND
RNA VIRUS
MINUS STRAND
RNA VIRUSES
REOVIRUS
(PATHOGEN OF PLANTS
AND ANIMALS)
ORTHOMYXOVIRUS
(CAUSES INFLUENZA
AND OTHER DISEASES
IN ANIMALS)
HOST CELL
RHABDOVIRUS
(CAUSES RABIES,
VESICULAR STOMATITIS
AND OTHER DISEASES
IN ANIMALS)
DOUBLE-STRAND
DNA VIRUSES
SINGLE-STRAND
DNA VIRUS
INOVIRUS
(PATHOGEN
OF BACTERIA)
ADENOVIRUS
(CAUSES TUMORS
AND OTHER DISEASES
IN ANIMALS)
MYOVIRUS
(PATHOGEN
OF BACTERIA)
43
00
10
11
01
100
000
110
010
1000
1100
0100
0000
101
1110
111
0001
001
011
0010
44
0101
0110
1111
1011
0011
1101
1001
1010
0111
would continuously replace the existing wild type in the population. The genome of a species would therefore drift
steadily but randomly through a certain
volume of sequence space.
Despite those dierences, both the
classical Darwinian and the neutralist
theories favor the idea that wild-type
populations will localize sharply in sequence space after completing an advantageous or neutral shift. Also, both
theories assume that mutations appear
blindly, irrespective of their selective value. No single neutral or advantageous
mutation would occur more frequently
than any disadvantageous one.
That view, however, is not sustained
by the modern kinetic theory of molecular evolution, nor is it backed by experiments with viruses. After all, evolutionary selection is a consequence of
the ability of a genome to replicate itself accurately. Imagine a case in which
the process of replication is so highly
error-prone that no copy resembled its
parental sequence. The resulting population would behave like an ideal gas,
expanding until it lled the sequence
space at a very low density. Selection
acting on such a population could not
dene it or conne it in any way. The
population would lose all its integrity.
If we were to reduce the error rate of
replication progressively, variation in the
population would disperse less and less
as the ospring came to resemble their
parents more and more. At some critical error rate, the eect of selection on
ecause the error rate directly determines the size and integrity of
a quasispecies, it is the most telling characteristic of a virus. The error
rate is the probability that an error will
occur when one nucleotide in a sequence
is being copied. It can depend both
on the type of nucleotide substitution
taking place and on its position in the
PERFECT REPLICATION
OF WILD TYPE
HIGHLY IMPERFECT
REPLICATION
sequence. The position is important because the ribosome interprets the nucleotides three at a time, in a group
called a codon. In most codons the rst
two positions sufce to specify the amino acid to be incorporated into a protein. Mutations in the rst two positions
may therefore be more stringently maintained by selection. When researchers
speak of the error rate of an entire viral
sequence, they are referring to an average for all the positions.
In general, the error rate of a virus is
roughly proportional to the reciprocal
of its sequence lengththat is, about
one error per replicated sequence. If the
error rate were much larger, almost every replication event would produce an
unt mutation. For an entity that produces as many ospring as a virus, an
error rate reciprocal to the sequence
length is highly signicant. Consider a
typical infection process, which starts
when at least one viable virus enters a
host organism. If that virus is not eradicated, it will replicate. Before an infection is detectable, the viral population
must rise to around 109, which would
take about 30 generations. If the error
rate is more or less equal to the reciprocal of the sequence length, then on
average one error will have been added
in each generation.
Consequently, any two viruses taken
from an obviously infected host are likely to dier from each other at 30 nucleotide positions or more. When researchers rst noticed the sequence diversity of the HIV viruses they found in
individual patients, they thought it was
evidence of multiple infections by different strains. The work of Simon Wain
Hobson of the Pasteur Institute in Par-
QUASISPECIES
45
RAND RNA
ND RNA
RA
S ST
ST
OF
PLU
MIN
US
3'
REL
EA
SE
5'
3'
A
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ND
RA
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PL
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IN
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T
PL O M
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ST US S
RA TR
ND AND
RN
A
RE
LE
E
AS
OF
5'
O
F
CO
AT
5'
RELEASE
OF
5'
5'
PR
OT
EIN
PL
U
OF
RE
LE
AS
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3'
5'
OF SYN
CO THE
SI
AT
PRO S
TEIN
FO
RM
SUBU
NITS
CO
MB
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TO
RN
A
5'
3'
A
RN
ND
RA NA
ST D R
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PL ST
S
REP
LIC
AND ASE
MA BIN
KE DS
S
M TO
IN
U
A
RN
ND
A
R
ST
EIN
OT NA
PR D R
AT RAN
CO ST
S
U
RE
+ 3
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AS
IC
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P
5'
T
NI
IS
ES BU
TH SU
SYN ASE
IC
EPL
OF R
RIB
INF OSO
OR M
MA E B
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ON D
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RIB
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ION
MAT
ME B
INDS TO R LICASE INFOR
EP
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3'
5'
A
LE
RE
3'
RIBOSOME
REPLICASE
REPLICASE SUBUNIT
COAT PROTEIN
back loops that describes a regulated coevolution within a cell of the viral genes
and the viral proteins essential to replication that are encoded by those genes.
Michael Gebinoga of the Max Planck Institute for Biophysical Chemistry in Gttingen has quantied the process in vivo
for the Q bacteriophage. He found evidence of two feedback cycles, one based
on the enzyme replicase, which promotes replication, and the other based
and I have taken that approach. We developed a mathematical method of analyzing the relations within a quasispecies that we call statistical geometry in
sequence space. That analysis allows
us to determine how often on average
dierent types of changes occur at different positions. It enables us to classify
dierent positions in the viral sequences as constant, variable or hypervariable. From that information, we can deduce roughly how long dierent viral
lineages have existed and the frequency with which dierent types of mutations occur.
hat do the statistical geometries of the inuenza A, polio1 and immunodeciency viruses reveal? For the tree of inuenza A
virus, the probability of mutations that
would parallel or reverse previous changes is small. As Paleses study indicated,
the amount of dierence between strains
of the virus increases almost linearly
over time. An intriguing prediction also
emerges from the data: if all the mutable positions in the virus continue to
change at the indicated rates, the inuenza virus should completely lose its
identity within a few hundred years. Because some positions must be constant,
the inuenza A virus will probably remain a pathogen, because to survive, it
will need to infect humans, but we cannot predict what its pathology will be.
For polio-1 virus, the picture is entirely dierent. In the studied sequence
segment, the nucleotides that occupy
the rst and second positions in each
codon scarcely change at all. Mutations
at those positions must be strongly eliminated from the quasispecies by selection. Conversely, the nucleotides at the
third codon positions are almost completely randomized. As a result, even
though the poliovirus has about the
same error rate as the inuenza virus,
only mutations that do not change the
encoded amino acids appear in the quasispecies. The proteins in the poliovirus are very highly conserved.
The immunodeciency viruses have
a third type of statistical geometry. All
three codon positions are appreciably
randomized for all types of changes. We
have been able to determine the prevalence of constant, variable and hypervariable sites within the gene for an HIV
surface protein that we analyzed. From
that information, we were able to estimate how long it must have taken for
the immunodeciency viruses to have
diverged to the observed degree.
About 20 percent of the positions are
constant, apparently because they are
necessary for HIV to function as a retrovirus. They establish that HIV is the
SCIENTIFIC AMERICAN July 1993
47
STIRRING
CONTROL
COMPUTER
TURBIDITY
CONTROL
PUMP
NUTRIENT
SOLUTION
PUMP
FERMENTER
FLOW REACTORS
EVOLUTION MACHINES of various types are used in the authors laboratory to study the evasive changes that virus populations can make when subjected to selection pressure. The
machines create systems of cell cultures in which viruses grow
under tightly controlled conditions for many generations. Nutrient solution is pumped into a fermenter in which grow host
cells, such as the bacteria Escherichia coli. These cells are then
COLLECTED
SAMPLES
the host. Yet by the time those mutations occur, the immunologic protection
of the host is already practically perfect. The success of the Sabin vaccine
in saving the lives of countless children
is unchallenged.
Inuenza is a quite dierent case, as
are other viruses. The targets for the immune response against inuenza change
steadily. Although the immune system
eventually copes with the virus and
quells the infection, there is no lasting
protection. As a consequence, people
can contract inuenza repeatedly, and
new vaccines must be prepared every
few years. John J. Holland of the University of California at San Diego and Esteban Domingo of the Independent University of Madrid have observed that the
viruses responsible for foot-and-mouth
disease and vesicular stomatitis, an infection of the oral membranes in livestock, behave in a similar way. HIV, with
its many variable and hypervariable positions, mutates even more rapidly and
radically. Vaccines may not have any
lasting value against such infections.
But vaccines are only one way to ght
viruses. The administration of drugs that
block viral replication is an extremely
common therapyand for AIDS it is
currently the sole therapy that is in any
way eective at slowing the progress of
the disease. In theory, articial chains
of RNA could be administered to patients to prevent or eliminate viral infections. Those RNA molecules would
hinder viral replication, either by binding to the viral RNA or by competing
with it for essential enzymes. Specic
factors that interfere with viral replication could also be incorporated into host
cells by genetic technology. Yet all these
approaches may have harmful side effects or would need to clear signicant
technical hurdles.
A further complication is that viruses may be able to mutate around such
obstacles. In my laboratory Bjrn F. Lindemann has used the understanding of
the replicative mechanism of the Q bacteriophage to test one antiviral strategy. He inserted the gene for the viral
coat protein into cells. The cells became resistant to infection because the
coat protein, a natural regulator of the
phages replication, blocked the transcription of viral genes.
Yet this strategy did not work perpetually : given sucient time and generations, the Q bacteriophage adapted by
mutating into a form that ignored the
coat protein signal. Lindemann demonstrated that fact using one of the automated evolution machines developed
recently in my laboratory. In these devices, viruses grow in host cells for extended periods under mild selection
VACCINATION has been extremely eective in controlling polio and some other
diseases. Because the proteins of poliovirus change very little over time, it is relatively easy to nd consistently good immunologic targets. Against more mutable
viruses, such as the AIDS virus, vaccination is much less potent.
origin of viruses or their role in the evolution of the biosphere. Viruses come
and go: some adapt; others disappear.
The undeniable reality is that an estimated 13 million people worldwide are
infected with HIV. Pandoras box is still
open and releasing new ills. Nevertheless, our growing understanding of viruses suggests that, as in the original
myth, hope has not escaped.
FURTHER READING
MOLECULAR QUASI-SPECIES. Manfred Eigen, John McCaskill and Peter Schuster
in Journal of Physical Chemistry, Vol.
92, No. 24, pages 68816891; December 1, 1988.
ROLE OF GENOME VARIATION IN VIRUS
EVOLUTION. Manfred Eigen and Christof K. Biebricher in RNA Genetics, Vol.
3: Variability of RNA Genomes. Edited
by Esteban Domingo, John J. Holland
and Paul Ahlquist. CRC Press, 1988.
HOW OLD IS THE IMMUNODEFICIENCY VIRUS? Manfred Eigen and Katja NieseltStruwe in AIDS, Vol. 4, Supplement 1,
pages S85S93; 1990.
STATISTICAL GEOMETRY ON SEQUENCE
SPACE. Manfred Eigen and Ruthild Winkler-Oswatitsch in Molecular Evolution:
Computer Analysis of Protein and Nucleic Acid Sequences. Edited by Russell
F. Doolittle. Academic Press, 1990.
THE HYPERCYCLE: COUPLING OF RNA
AND PROTEIN BIOSYNTHESIS IN THE INFECTION CYCLE OF AN RNA BACTERIOPHAGE. M. Eigen, C. K. Biebricher, M.
Gebinoga and W. C. Gardiner, Jr., in Biochemistry, Vol. 30, No. 46, pages 11005
11018; November 19, 1991.
49
LEAELLYNASAURA
pears to have been within the temperate range, yet the sun did not shine
throughout the long winter.
Many dinosaur lineages survived in
this strange environment after they had
died out in other places. At least one
member of the group evolved an adaptation to the cold and to the dark that
is interesting both in itself and for what
it tells of the passing of a biological
epoch. If global cooling indeed killed the
ALLOSAURUS
AUSTRALIAN DINOSAURS ourished in southeastern Victoria during the Early Cretaceous, when the region lay within
50
MUTTABURRASAURUS
the Antarctic Circle. This mural depicts six species that left
fossils there and a sevenththe large iguanodontid Muttabur-
PTEROSAUR (FLYING)
ANKYLOSAUR
ATLASCOPCOSAURUS
ORNITHOMIMOSAUR
51
EQUATOR
AUSTRALIA
TODAY
T
RC
IRCLE
IC C
DINOSAUR
COVE
AN
TA
108 MILLION
YEARS AGO
ancient lake. This inland site has therefore yielded some uncommonly well preserved specimens.
It must be noted that southeastern
Australias dinosaurs are known from a
mere 5,000 individual bones and two
partial skeletons. Just a few hundred of
the bones can be assigned to a given
species or genus. What they lack in number, however, they make up in scientific interest.
All eorts at interpretation revolve
around the estimation of temperature,
for which two methods have been tried.
Robert T. Gregory of Southern Methodist University and his associates infer
Australian paleoclimate from the ratio
of oxygen 18 to oxygen 16 trapped in
ancient rocks. They nd that mean annual temperatures probably approached
zero degrees Celsius but might have
reached as high as eight degrees C above
zero. Such values occur today in Hudson Bay, Saskatchewan (zero degrees C),
and in Minneapolis and Toronto (eight
degrees C above zero).
Robert A. Spicer of the University of
Oxford and Judith Totman Parrish of
the University of Arizona instead deduce temperature from the structure
of ancient plants, arriving at the somewhat higher mean annual temperature
of 10 degrees C. Their research has
demonstrated that polar Australia supported conifers, ginkgoes, ferns, cycads,
bryophytes and horsetails but only a
few angiosperms, or owering plants,
identiable by a sprinkling of pollen.
The angiosperms were then just beginning to spread into new niches. Perhaps they got their start by exploiting
weedy ecological systems in the rift val52
absolute and relative peak in the Victorian sediments. Not only do hypsilophodontids constitute most of the dinosaur remains, they are also represented
by four to ve genera, depending on the
taxonomic criteria one uses, and ve to
six species. Other areas, some much
more richly endowed with dinosaur species, never harbored more than three
kinds of hypsilophodontids at a time.
Something clearly favored the diversication of this group in polar Australia.
inate an environment marked by seasonal darkness. This hypothesis may also explain the huge optic lobes, of which the
left one can be seen at the rear of this natural brain cast (below; bump at far right), formed when silt solidied in the skull.
53
al Geographic Society). The brain, unusually large for a dinosaur of this size,
bears the marks of optic lobes whose relative size is easily the greatest ever documented in a hypsilophodontid.
How is one to interpret these enlarged
lobes? We hypothesize that they enhanced the animals ability to see in the
dark, enabling them to forage eectively during the long winter months. There
would have been no lack of food then,
for those capable of seeing it: the herbivores could have lived o evergreens
and deciduous leaf mats, and the carnivores could have hunted the herbivores.
This hypothesis also explains why this
group came to dominate the polar environment in the rst place. Hypsilophodontids everywhere in the world had
large eyes and, presumably, acute vision.
That trait could have given them their
foothold in polar Australia. Once estab-
54
HARD ROCK makes hard work for these volunteer paleontologists. Full-scale mining techniques (left ) and explosives (right)
dinosaurs to lower latitudes in the Cretaceous of Australia may be real or merely an artifact of sampling. We worry
about this question because the oodwaters that broke out of rain-swollen
rivers would have collected small and
medium-size bones but left large ones.
The body of a sauropod would have
stayed put rather than oating to a place
where many specimens were concentrated in the small ood channels, which
were no more than ve to 10 meters in
width and 20 to 30 centimeters in depth.
Yet we suspect there was an underlying tendency toward small body size in
these polar environs. None of the hypsilophodontids, it must be remembered,
stood taller than a human, and most
were barely knee-high. The dwarf Allosaurus matches the smallest we have examined in the North American collections. The ornithomimosaur is equally
unprepossessing, and the protoceratopsid and the ankylosaur are no bigger than a sheep. A single fragment of
a claw constitutes our sole record of a
forma carnivore, apparently similar
to Baryonyx of Englandwhich may
have measured up to eight meters in
length.
This pattern contradicts the scaling
laws that Bergmann and Allen formulated in the 19th century. According to
these laws, animals in a given lineage
tend to become larger and more compact as the average temperature of their
environment falls. This trend is exemplied by the comparison of mountain
lions in Canada with pumas of Central
America and of human populations in
the subarctic and tropical zones.
Other factors also determine body
dimensions, especially the size of the
territory in which a population lives.
Individuals found on islands are often smaller than their mainland counterparts. For example, there were dwarf
elephants on the ancient Mediterranean
articial winter could have killed the dinosaurs unless it lasted for a long time,
certainly more than a few months. Otherwise at least a few of the polar dinosaurs would have survived the cataclysm. Of course, it is possible that some
other development had already ended
the reign of southern Australias dinosaurs by the end of the Cretaceous.
Arthur Conan Doyle once dreamed
of a plateau in South America that time
forgot, where dinosaurs continued to
reign. Reports earlier this year that
dwarf mammoths survived to early historical times, in islands o the coast
of Siberia, give force to such speculation. If dinosaurs found a similar haven
in which they outlived the rest of their
kind, then we think polar Gondwana,
including southeastern Australia, is a
likely place to look for it.
FURTHER READING
EVIDENCE FOR LOW TEMPERATURES AND
BIOLOGIC DIVERSITY IN CRETACEOUS
HIGH LATITUDES OF AUSTRALIA. P. V.
Rich, T. H. Rich, B. E. Wagstaff et al. in
Science, Vol. 242, pages 14031406; December 9, 1988.
OXYGEN ISOTOPIC COMPOSITION OF CARBONATE CONCRETIONS FROM THE LOWER CRETACEOUS OF VICTORIA, AUSTRALIA. R. T. Gregory, C. B. Douthitt, I. R.
Duddy et al. in Earth and Planetary Science Letters, Vol. 92, No. 1, pages 27
42; February 1989.
POLAR DINOSAURS AND BIOTAS OF THE
EARLY CRETACEOUS OF SOUTHEASTERN
AUSTRALIA. T. H. Rich and P. V. Rich in
National Geographic Research, Vol. 5,
No. 1, pages 1553; Winter 1989.
CONTINENTAL CLIMATE NEAR THE ALBIAN SOUTH POLE AND COMPARISON
WITH CLIMATE NEAR THE NORTH POLE.
J. T. Parrish, R. A. Spicer, J. G. Douglas
et al. in Geological Society of America,
Abstracts with Programs, Vol. 23, No. 5,
page A302; Annual Meeting, 1991.
55
56
TRAPPED MERCURY IONS, separated by about 10 microns, uoresce under illumination by ultraviolet light (photograph).
The ions are held by oscillating electric elds generated by
electrodes (cutaway diagram). Static electric potentials (not
shown) prevent the ions from escaping through the ends of
the trap. Strings of trapped ions may lead to new timing devices more stable than conventional atomic clocks.
57
58
Resonance Frequency
levels, and so fewer will strike the detector. One knows, therefore, that the
applied microwaves match the natural
frequency of the atoms if the number
of atoms striking the detector is maximal. An electronic feedback mechanism, called a servo loop, keeps this
value constant. If it nds that the current from the detector is falling o, it
changes the frequency of the applied
eld until the current reaches a maximum again.
By keeping the current from the detector at a maximum, the servo loop
maintains the frequency of the applied
microwave eld at the natural frequency of the atoms. To measure time, one
couples the applied eld to a frequency divider, which generates timing pulses. By analogy, the atoms represent the
quartz crystal in a watch or the master
pendulum in a Shortt clock. The applied microwave eld is the oscillating
circuit or the slave pendulum, which
actually drives the clock mechanism.
Minor variations of the atomic beam
standard exist. For example, in some devices the atoms that undergo a change
in energy level are made to miss, rather than strike, the detector. Not much
dierence in accuracy exists, however.
Rather all the versions to some extent
represent trade-os in terms of size,
cost and complexity.
A more important modication of
the atomic beam came in 1949, when
one of us (Ramsey) invented the socalled separated oscillatory eld method. Instead of irradiating the atoms
with a single applied eld, this technique relies on two elds, separated by
some distance along the beam path. Applying the oscillating eld in two steps
has many benets, including a narrowing of the resonance and the elimination
of the rst-order Doppler shift. Jerrold
R. Zacharias of the Massachusetts Institute of Technology and Louis Essen and
John V. L. Parry of the National Physical Laboratory in Teddington, England,
adapted this method to working frequency standards in the mid-1950s.
Currently the separated oscillatory
eld method provides the most reproducible clocks. The best ones are located at a few national laboratories, although smaller and less accurate versions are commercially available. The
clocks rely on cesium, which has several
advantages over other elements. It has a
relatively high resonance frequency
about 9,192 megahertzand low resonance width, which lead to an excellent
Q . Cesium can also be detected readily
and eciently; all that is needed is a hot
metal lament. When a cesium atom
strikes the lament, it ionizes and becomes observable as electric current.
f
PHOTON
E1
59
DETECTOR
MAGNET B
MAGNET A
MICROWAVE
CAVITY
SOURCE
SERVO
MECHANISM
MICROWAVES
DIGITAL COUNTER
AND DISPLAY
FREQUENCY
DIVIDER
ATOMIC-BEAM frequency standards provide the most accurate, long-term timekeeping. Conventional atomic clocks rely on magnets (a). Atoms in the correct energy level are deected by magnet A through the microwave cavity. Microwave elds oscillating at the resonance frequency of the atoms drive some of them into a second energy level. These atoms are deected by magnet B so as to strike a detector. The
servo mechanism monitors the detector and maintains the frequency of the applied
microwaves at the resonance frequency. To keep time, some of the microwaves are
TUNED CAVITY
MICROWAVE
PHOTONS
DIGITAL COUNTER
AND DISPLAY
MAGNET
SOURCE
highest stability of any frequency standard, better than one part per 10 15.
Unfortunately, the masers superior
attributes last just for a few days. Beyond that, its performance falls below
that of cesium beams. The stability decreases because of changes in the cavitys resonant frequency. Collisions between the atoms and the bulb shift the
frequency by about one part per 10 11.
One way to overcome the problem is
to operate the hydrogen maser at low
temperatures. This condition allows
more atoms to be stored (thus resulting
in a stronger signal) and reduces electronic noise. Coating the inside of the
bulb with superuid liquid helium also
enhances performance. This substance
acts as a good surface against which the
hydrogen atoms can bounce. More eective magnets, better coating substances
and servo loop techniques that keep the
cavity resonance centered on the atomic resonance are other approaches now
being taken to improve maser stability.
62
FREQUENCY
DIVIDER
STORAGE BULB
b
DETECTOR
MICROWAVE
CAVITY
SOURCE
LASER B
SERVO
MECHANISM
LASER A
MICROWAVES
DIGITAL COUNTER
AND DISPLAY
FREQUENCY
DIVIDER
directed to a device that divides the frequency into usable timing pulses. Optically
pumped standards (b) use light rather than magnets to select atoms. Laser A pumps
the atoms into the right energy level, preparing them to be excited by the microwaves. Only atoms placed in the correct energy level by the microwaves absorb light
from laser B. They quickly reemit that energy, which is sensed by a photodetector.
An optically pumped clock using cesium atoms at the National Institute of Standards
and Technology, called NIST-7, now keeps time for the U.S. (photograph).
63
LASER
he variety of high-performance
frequency standards that exist
today might seem to obviate the
need for future devices of even greater
performance. After all, current atomic
clocks are so accurate that they have
redened some of our basic units. As
mentioned earlier, the second is now
based on the resonance frequency of
the cesium atom. Also by international
agreement, the meter is dened as the
distance light travels in 1/299,792,458
of a second. The voltage unit is maintained by the characteristic frequency
associated with a voltage that appears
in a so-called Josephson junction in a
superconducting circuit.
There are, however, applications that
tax the capacity of modern clocks. Radio astronomy is a good example. Astronomers often use several telescopes
spaced thousands of kilometers apart
LASER
MICROWAVE
CAVITY
MICROWAVES
LASER
LASER
4
LASER
DETECTOR
LASER
ATOMIC FOUNTAIN uses atoms that have been cooled and trapped by six
laser beams (1). The vertical beams then briey impart an upward velocity
to the atoms. The atoms rise, passing through the microwave cavity on the
way up (2) and again on the way down (3). The rest of the process resembles optically pumped atomic-beam standards: the atoms pass through another laser beam (4 ), and their uorescence is recorded by a photodetector
(5 ). Servo loops and frequency dividers (not shown) generate timing pulses.
64
PROBE
LASER
INTERNATIONAL
DATELINE
MERIDIAN
OF GREENWICH
10
6 5
4 3
+1
+2
+3
+4
+5
+6
+7
+8
+9 +10 +11
+12
12
racy of about 100 meters because of deliberate scrambling of the signals transmitted from the satellites. A full complement of 24 satellites would give 24hour, worldwide coverage. The system
is nearly complete.
These and other applications show
the importance of time and frequency standards. The anticipated improvements in standards will increase the effectiveness of the current uses and open
the way for new functions. Only time
will tell what these uses will be.
FURTHER READING
pages 301320; September/October 1983.
FROM SUNDIALS TO ATOMIC CLOCKS: UNPRECISE MEASUREMENT OF TIME. N. F. RamDERSTANDING TIME AND FREQUENCY. J.
sey in American Scientist, Vol. 76, No. 1,
Jespersen and J. Fitz-Randolph. Dover,
pages 4249; January/February 1988.
1982.
TIME AND FREQUENCY. Special issue of ProHISTORY OF ATOMIC CLOCKS. N. F. Ramceedings of the IEEE, Vol. 79, No. 7; July
sey in Journal of Research of the Nation1991.
al Bureau of Standards, Vol. 88, No. 5,
65
Surgical Treatment
of Cardiac Arrhythmias
To save the life of a doomed patient, the author and his colleagues
developed a now standard surgical procedure for correcting
lethally fast heartbeats in many people susceptible to them
by Alden H. Harken
68
ventricle and, from there, out to the aorta, which distributes it to every part of
the body.
The signal giving rise to these machinations emanates from a cluster of conduction tissue cells collectively known
as the sinoatrial node. This node, located at the top of the right atrium, establishes the tempo of the heartbeat; hence,
it is often referred to as the cardiac pacemaker. It sets the tempo simply because
it issues impulses more frequently than
do other cardiac regions, once about every 830 milliseconds. If something provoked another part of the heart to re
at a faster rate, as occurred in the banker, it would become the new pacemaker. Although the sinoatrial node can respond to signals from outside the heart,
it usually becomes active spontaneously. In other words, it is on automatic pilot, a capability known as automaticity.
Such automaticity stems from the
unique leakiness of the membrane encasing nodal cells. As is true of the membrane surrounding muscle cells and neurons, the nodal cell membrane is studded with pumps that transport ions into
and out of the cell. The net result of this
exchange is the creation of an electrical
potential, or unequal charge distribution, across the membrane. Yet unlike
muscle and nerve cells, which maintain
their resting potential until they are
jogged by an outside stimulus, nodal
cells allow certain ions to leak back out
of the cells. This outow reduces the
membrane potential to a critical value.
At that point, the membrane permits a ood of other ions to rush back
into the cells. This onslaught momentarily depolarizes the cells (eliminates
the membrane potential) and actually
reverses the membrane polarity. Such
depolarization constitutes an impulse.
After the impulse is generated, cells
SCAR TISSUE
INCISION
CLAMP
AREA
BEING
EXCISED
CLAMP
SURGICAL
SCISSORS
apex) and, from there, up along the inner surface of the external (lateral) walls
to the top of the ventricle.
As impulses from the conduction bers reach muscle, they activate the overlying cells. Muscle cells, too, are capable
of relaying impulses, albeit more slowly than do conduction bers. The cells
of the endocardium (the inner surface
of the wall ) depolarize rst and relay
AORTA
LEFT
PULMONARY
VEINS
SINOATRIAL
NODE
LUNG
INFERIOR
VENA
CAVA
FT
LE RIUM
AT
HT
LVE
VA
M
RIU
AT
SE
ATRIOVENTRICULAR
NODE
E
CL
FT
LE NTRI
E
V
LV
VA
specialized electrical conduction system (green in large heart) normally regulates the steady beating of the
heart. The impulses (black arrows in
image at right) that induce pumping are
issued at set intervals from the sinoatrial node (large green oval at top left), or
the cardiac pacemaker. From there,
they race to the atrioventricular node
(above the ventricles) and, after a brief
pause, speed down along the septum
to the bottom of the heart and up its
sides. Meanwhile the impulses also migrate from the conduction fibers across
the overlying muscle, from the endocardium to the epicardium, thereby triggering the contractions that force blood (arrows in small diagram above) through
the heart and into the arterial circulation. The spread of electricity through a
healthy heart gives rise to the familiar
electrocardiogram at the bottom right.
The P wave (purple) and QRS wave (red )
form as impulses pass through the atria
and ventricles, respectively; the T wave
(black) arises as cardiac cells, which cannot be stimulated for a while after they
fire, recover their excitability.
70
UM
PT
RIG
LATERAL
WALL
HT CLE
RIG NTRI
VE
CONDUCTION
BUNDLE
ENDOCARDIUM
EPICARDIUM
PURKINJE
FIBER
APEX
Q
S
efore proceeding, we had to develop a way to locate the renegade pacemaker. We hoped we
might nd it by analyzing signals reaching an electrode placed directly on the
inner or outer surface of the heart [see
bottom illustration on next page]. More
specically, we planned to induce sustained tachycardia with a pacing electrode. During each heartbeat, we would
measure electric currents produced at
a single site (consisting of a small cluster of cells) along the diseased border
of the heart attack scar. We would start
at a position arbitrarily designated as
12 oclock and proceed around the
clock face back to the beginning.
We would delineate the circuit by
comparing the time of electrical activation in each region against that seen in
healthy tissue. Regions that generated
currents before the healthy tissue did
would be revealed as belonging to the
circuit; the area that became excited earliest would be the pacemaker. We could
not rely on standard electrocardiography for this purpose because it lacked
the specicity we needed. Familiar electrocardiogram tracings, made by attaching electrodes to the skin, reect the
summed activity of many thousands of
71
DISEASED
CELLS
DEAD
CELLS
2
IM
S
UL
ES
PASSING AROUN
DP
AT
C
BLOCKADE
ENTRYWAY
WAVE
OF IMPULSES TO REENTRANT CIRCUIT
REENTRANT CIRCUIT, a closed loop through which impulses can cycle repeatedly,
has formed in a patch of cardiac muscle populated by diseased tissue (beige) and
islands of dead cells (brown). Continuous electrical activity in such a circuit can
usurp the normal pacemaker function of the sinoatrial node, leading to ventricular
tachycardia (a dangerously fast heartbeat). Persistent cycling begins when a wave
of impulses (blue arrows in 1 ) enters the patch and divides (2 ) at the entryway. If
RECEDING
IMPULSES
IMPULSES
REENTERING CIRCUIT
signals owing along one pathway (two-headed black arrow) encounter a temporary blockade (vertical lines), those propagating along a second pathway (thin blue
arrow) may return to the entryway (3 ), or origin, through the previously blocked
alley. If the entryway has regained excitability (4 ), the returning impulses will reexcite that area. They may thus fan out through healthy muscle (large green arrows)
and proceed back through the worrisome circuit again and again (thin green arrow).
Yet we still faced two signicant puzzles, one scientic and one clinical. Why
is it that reentrant circuits do not become active every time the heart beats
in susceptible patients? In other words,
why can people often survive for months
or years before deadly disturbances of
rhythm arise? We also wondered how
we might noninvasively identify patients at risk for reentrant tachycardia
6
7
8
ur second problemreadily
identifying patients at risk for
reentrant tachycardiawas resolved masterfully by our co-worker
Michael B. Simson, a person of many
talents. Aside from being a superb cardiologist, he is, as I sometimes say, an
enthusiastic sports-car hack and computer driver. Steering his beat-up sports
car home one night after sitting in on
one of our surgical research meetings,
he began to ponder the electrical noise,
or seemingly random signals, emanating from the hood of his car. If he simply monitored the currents reaching the
hood, he reasoned, the resulting data
would be indecipherably chaotic. But if
he wanted to track the electrical impulses coming specically from his distributor, he might well discern them by
signal averaging.
In this procedure, he would record
the voltage and direction (the electrical
vector) of currents owing toward and
9
10
11
12
TIME (MILLISECONDS)
CARDIAC MAPPINGperformed by moving an electrode (blue) over diseased tissue surrounding a heart attack scarenables a surgeon to identify a reentrant circuit. In one patient, recordings of electrical activity (tracings at right) made at 12
sites (inset at left) around the inner surface during induced ventricular tachycardia
delineated a large, recurring electrical circuit that began at the one oclock position
(tracing 1) and progressed clockwise around the circumference of the scar. A surgeon can block impulse propagation in such a circuit by excising the region of earliest excitation, which can be assumed to be the entryway to the circuit.
73
160
BEFORE SURGERY
AFTER SURGERY
MICROVOLTS
120
VENTRICULAR
EXCITATION
80
ELECTRICAL ACTIVITY
DURING NORMALLY
QUIET PERIOD
40
0
0
100
200
TIME (MILLISECONDS)
300
100
200
TIME (MILLISECONDS)
300
had earlier caused reentrant arrhythmia in one of our patients. Before surgery, Simson attached his new recorder
to the patient and noted, as expected,
that there was a urry of electrical activity in the usually quiescent span following ventricular excitation. But was
the signal, in fact, an indication of late
impulse conduction in a reentrant circuit? The answer would be yes if the
uctuations disappeared after the operation. The surgical procedure went
well. Josephson and Horowitz identied the circuit, and I excised the entryway. After surgery, Simson reattached
his device to the patient. The post-QRS
uctuations were gone.
We had come a long way since 1978.
We had learned why our surgical approach, initially designed by guesswork,
is useful. It interrupts the diseased anatomic pathway that, in response to aberrant ring by a nearby cell, gives rise to
the repeated ow of impulses through
a recursive circuit. Moreover, we had
gained the ability to identify noninvasively patients at risk.
FURTHER READING
OBSERVATIONS ON MECHANISMS OF VENTRICULAR TACHYCARDIA IN MAN. H.J.J.
Wellens, D. R. Duren and K. I. Lie in Circulation, Vol. 54, No. 2, pages 237244;
August 1976.
SURGICAL ENDOCARDIAL RESECTION FOR
THE TREATMENT OF MALIGNANT VENTRICULAR TACHYCARDIA. A. H. Harken,
M. E. Josephson and L. N. Horowitz in
Annals of Surgery, Vol. 190, No. 4, pages 456460; October 1979.
CARDIAC ARRHYTHMIAS. A. H. Harken
in Care of the Surgical Patient, Vol. 1:
Critical Care. Edited by D. W. Wilmore,
M. F. Brennan, A. H. Harken, J. W. Holcroft and J. L. Meakins. Scientic American Medicine, 1992.
Fuzzy Logic
The binary logic of modern computers often falls short
when describing the vagueness of the real world.
Fuzzy logic oers more graceful alternatives
by Bart Kosko and Satoru Isaka
76
the core of modern set theory and logic. According to the old riddle, a Cretan
asserts that all Cretans lie. So, is he lying? If he lies, then he tells the truth
and does not lie. If he does not lie, then
he tells the truth and so lies. Both cases lead to a contradiction because the
statement is both true and false. Russell found the same paradox in set theory. The set of all sets is a set, and so it
is a member of itself. Yet the set of all
apples is not a member of itself because its members are apples and not
sets. Perceiving the underlying contradiction, Russell then asked, Is the set
of all sets that are not members of themselves a member of itself? If it is, it isnt;
if it isnt, it is.
Faced with such a conundrum, classical logic surrenders. But fuzzy logic says
that the answer is half true and half
false, a 5050 divide. Fifty percent of
the Cretans statements are true, and
50 percent are false. The Cretan lies 50
percent of the time and does not lie the
other half. When membership is less
than total, a bivalent system might sim-
steam engine. Since then, the term fuzzy logic has come to mean any mathematical or computer system that reasons with fuzzy sets.
77
SET THEORY underlies the dierence between standard and fuzzy logic. In standard logic, objects belong to a set fully or not at all (top left ). Objects belong to a
fuzzy set only to some extent (top right ) and to the sets complement to some extent. Those partial memberships must sum to unity (bottom). If 55 degrees is 50
percent cool, it is also 50 percent not cool.
uzzy products use both microprocessors that run fuzzy inference algorithms and sensors that
measure changing input conditions.
Fuzzy chips are microprocessors designed to store and process fuzzy rules.
In 1985 Masaki Togai and Hiroyuki Watanabe, then working at AT&T Bell Laboratories, built the rst digital fuzzy
chip. It processed 16 simple rules in
12.5 microseconds, a rate of 0.08 million fuzzy logical inferences per second.
Togai InfraLogic, Inc., now oers chips
based on Fuzzy Computational Acceleration hardware that processes up to two
million rules per second. Most microprocessor rms currently have fuzzy
chip research projects. Fuzzy products
largely rely on standard microprocessors that engineers have programmed
with a few lines of fuzzy inference code.
Although the market for dedicated fuzzy chips is still tiny, the value of microprocessors that include fuzzy logic already exceeds $1 billion.
The most famous fuzzy application
is the subway car controller used in
Sendai, which has outperformed both
human operators and conventional automated controllers. Conventional controllers start or stop a train by reacting
to position markers that show how far
the vehicle is from a station. Because
the controllers are rigidly programmed,
the ride may be jerky : the automated
controller will apply the same brake
pressure when a train is, say, 100 meters from a station, even if the train is
going uphill or downhill.
In the mid-1980s engineers from Hitachi used fuzzy rules to accelerate,
slow and brake the subway trains more
smoothly than could a deft human operator. The rules encompassed a broad
78
MEMBERSHIP
(PERCENT)
NONFUZZY SET
100
COOL
FUZZY SET
COOL
100
0
50
60
70
AIR TEMPERATURE
50
60
70
AIR TEMPERATURE
COOL
NOT COOL
MEMBERSHIP
(PERCENT)
100
50
0
50
60
70
AIR TEMPERATURE (DEGREES FAHRENHEIT)
BLAST
FUNCTION:
X
Y
IF WARM,
THEN FAST
FAST
MEDIUM
IF JUST RIGHT,
THEN MEDIUM
IF COOL,
THEN SLOW
SLOW
STOP
COLD
JUST
RIGHT
COOL
WARM
HOT
100
PERCENT
PERCENT
100
70
COOL
JUST
RIGHT
20
70
SUMMED SETS
MEDIUM
20
SLOW
0
50
60
68 70
AIR TEMPERATURE (DEGREES FAHRENHEIT)
80
APPLICATION OF FUZZY LOGIC to the control of an air conditioner shows how manipulating vague sets can yield precise instructions. The air conditioner measures air temperature and then calculates the appropriate motor speed. The
system uses rules that associate fuzzy sets of temperatures,
such as cool, to fuzzy sets of motor outputs, such as slow.
Each rule forms a fuzzy patch. A chain of patches can approx-
10
47
MOTOR SPEED (REVOLUTIONS PER MINUTE)
imate a performance curve or other function (top). If a temperature of 68 degrees Fahrenheit is 20 percent cool and 70
percent just right (bottom left), two rules re, and the system tries to run its motor at a speed that is 20 percent slow
and 70 percent medium (bottom right ). The system arrives
at an exact motor speed by nding the center of mass, or centroid, for the sum of the motor output curves.
79
1/2
ONE OBJECT
80
Depending on the available data, networks can learn patterns with or without supervision. A supervised net learns
by trial and error, guided by a teacher.
A human may point out when the network has erredwhen it has emitted a
response that diers from the desired
output. The teacher will correct the responses to sample data until the network responds correctly to every input.
Supervised networks tune the rules
of a fuzzy system as if they were synapses. The user provides the rst set
of rules, which the neural net renes
by running through hundreds of thousands of inputs, slightly varying the fuzzy sets each time to see how well the
system performs. The net tends to keep
the changes that improve performance
and to ignore the others.
A handful of products in Japan now
use supervised neural learning to tune
the fuzzy rules that control their operation. Among them are Sanyos microwave oven and several companies washing machines. Sharp employs this technique to modify the rules of its fuzzy
refrigerator so that the device learns
how often its hungry patron is likely to
open the door and adjusts the cooling
cycle accordingly. So far the neural net
must learn o-line in the laboratory,
from small samples of behavior by average customers. In time, researchers
at such groups as Japans Laboratory for
International Fuzzy Engineering and the
Fuzzy Logic Systems Institute hope to
build fuzzy systems that will adapt to
the needs of each consumer.
Supervised networks do have drawbacks. Tuning such systems can take
hours or days of computer time be-
SECOND OBJECT
Systems with fuzzy controllers are often more energy ecient because they
calculate more precisely how much power is needed to get a job done. Mitsubishi and Koreas Samsung report that
their fuzzy vacuum cleaners achieve
more than 40 percent energy savings
over nonfuzzy designs. The fuzzy systems use infrared light-emitting diodes
to measure changes in dust ow and so
to judge if a oor is bare. A four-bit microprocessor measures the dust ow to
calculate the appropriate suction power and other vacuum settings.
Automobiles also benet from fuzzy
logic. General Motors uses a fuzzy transmission in its Saturn. Nissan has patented a fuzzy antiskid braking system,
fuzzy transmission system and fuzzy
fuel injector. One set of fuzzy rules in
an on-board microprocessor adjusts the
fuel ow. Sensors measure the throttle
setting, manifold pressure, radiator water temperature and the engines revolutions per minute. A second set of fuzzy
rules times the engine ignition based on
the revolutions per minute, water temperature and oxygen concentration.
One of the most complex fuzzy systems is a model helicopter, designed
by Michio Sugeno of the Tokyo Institute of Technology. Four elements of
the craftthe elevator, aileron, throttle
and rudderrespond to 13 fuzzy voice
commands, such as up, land and
hover. The fuzzy controller can make
the craft hover in place, a dicult task
even for human pilots.
A few fuzzy systems manage information rather than devices. With fuzzy
logic rules, the Japanese conglomerate
Omron oversees ve medical data bases
2/3
(11) TOTAL
SET
A
CENTRAL
POINT
1/3
A*
(00)
1/4
EMPTY SET
3/4
(10)
FIRST OBJECT
daptive systems called neural networks can help fuzzy systems learn rules. A neural network accepts
pairs of input and output data, such as temperatures and
motor speeds for air conditioners, and groups them into
a small number of prototypes, or classes. Within the network, each prototype acts as a quantization vectora
list of numbersthat stands for the synapses feeding into
FIELD OF COMPETING
NEURONS
RULE PATCH
OUTPUT
SYNAPTIC VECTOR
QUANTIZATION
VECTOR
DATA POINT
INPUT
FURTHER READING
VAGUENESS: AN EXERCISE IN LOGICAL
ANALYSIS. Max Black in Philosophy of
Science, Vol. 4, No. 4, pages 427455;
October 1937.
FUZZY SETS AND APPLICATIONS: SELECTED PAPERS BY L. A. ZADEH. Edited by R.
R. Yager et al. Wiley-Interscience, 1987.
NEURAL NETWORKS AND FUZZY SYSTEMS.
Bart Kosko. Prentice-Hall, 1991.
PROGRESS IN SUPERVISED NEURAL NETWORKS. Don R. Hush and Bill G. Horne
in IEEE Signal Processing Magazine,
Vol. 10, No. 1, pages 839; January
1993.
81
Edwin Hubble
and the Expanding Universe
More than any other individual, he shaped
astronomers present understanding of an expanding
universe populated by a multitude of galaxies
by Donald E. Osterbrock, Joel A. Gwinn and Ronald S. Brashear
uring the 1920s and 1930s, Edwin Powell Hubble changed the
scientic understanding of the
universe more profoundly than had any
astronomer since Galileo. Much as Galileo banished the earth from the center
of the solar system, Hubble proved that,
rather than being unique, the Milky Way
is but one of untold millions of galaxies, or island universes. Hubbles work
also helped to replace the notion of a
static cosmos with the startling view
that the entire universe is expanding,
the ultimate extension of Galileos deant (if apocryphal) assertion, Yet still
it moves. Although many researchers
contributed to those revolutionary discoveries, Hubbles energetic drive, keen
intellect and supple communication
skills enabled him to seize the problem of the construction of the universe
and make it peculiarly his own.
Hubbles early years have become enmeshed in myth, in part because of his
desire to play the hero and in part because of the romanticized image of him
recorded by his wife, Grace, in her journals. Many accounts of Hubble conse-
84
breaking cosmological discoveries. He is seen here in the observing cage of the 200-inch Hale telescope, circa 1950.
ginning of the 20th century, many astronomers had come to believe that spiral nebulae were in fact distant galaxies
composed of a multitude of stars; skeptics continued to argue that these objects were nearby structures, possibly infant stars in the process of formation.
At the 1914 Astronomical Society
meeting, Slipher personally presented
the rst well-exposed, well-calibrated
photographs of the spectra of spiral nebulae. Those photographs displayed light
SCIENTIFIC AMERICAN July 1993
85
with his sister Lucy, a Red Cross nurse, captures his sense of
pride in uniform (top right ). Hubble often went on weekend
outings, such as this one with his high school students and
their family members (bottom left ). Late in life, he came to enjoy the solitary pleasures of y-shing (bottom right ).
EARTHBOUND
OBSERVER
GALAXY 1
1,000
INDIVIDUAL
GALAXIES
500
0
GROUPS
OF GALAXIES
0
106
2 X 106
DISTANCE (PARSECS)
GALAXY 2
CHANGE IN DISTANCE
CHANGE
IN DISTANCE
TIME 1
TIME 2
TIME 1
TIME 2
RELATIVE DISTANCE
87
out in full detail his studies of the distance to and stellar composition of M31.
In addition to determining the distance to the extra-galactic nebulae,
Hubble sought to classify them and to
comprehend their diversity of structure.
Starting in 1923, he ordered the nebulae according to a perceived pattern of
evolution. As an elliptical nebula ages,
Hubble argued, it forms arms that enlarge and open up. To explain the existence of barred spirals, in which the spiral arms trail from a barlike formation,
Hubble suggested that the elliptical
could evolve into either a normal spiral
or the barred form. The resulting double-pronged classication diagram is still
widely used, though stripped of its evolutionary implications.
SPIRAL GALAXY M33 was an early target of Hubbles eorts to determine the distance scale of the universe. Based on his observation of Cepheid variable stars in
M33, Hubble proved that it lies far beyond the known limits of the Milky Way and
hence must be an independent galaxy comparable to our own.
FURTHER READING
THE EXPANDING UNIVERSE: ASTRONOMYS
GREAT DEBATE, 19001931. Robert Smith.
Cambridge University Press, 1982.
MAN DISCOVERS THE GALAXIES. Richard
Berendzen, Richard Hart and Daniel Seeley. Columbia University Press, 1984.
THE OBSERVATIONAL APPROACH TO COSMOLOGY: U.S. OBSERVATORIES PRE
WORLD WAR II. Donald E. Osterbrock in
Modern Cosmology in Retrospect. Edited by R. Bertotti, R. Balbinot, S. Bergia
and A. Messina. Cambridge University
Press, 1990.
SELF-MADE COSMOLOGIST: THE EDUCATION OF EDWIN HUBBLE. Donald E. Osterbrock, Ronald S. Brashear and Joel
A. Gwinn in Evolution of the Universe of
Galaxies: Edwin Hubble Centennial Symposium. Edited by Richard G. Kron. Astronomical Society of the Pacic, 1990.
89
91
AMAZON RAIN FOREST extends into nine countries and covers 60 percent of Brazilsome 510 million hectares (about 1.3 billion acres).
92
EQUATOR
MACAPA
MANAUS
BELM
Paragominas
ACRE
RIO AMAZONAS
BRANCO
PAR
Xapuri
RONDNIA
Aukre
B R A Z I L
MATO
GROSSO
BRASLIA
RIO DE
JANEIRO
SO PAULO
PACIFIC
OCEAN
TROPIC
OF CAP
RICOR
N
PRTO
ALEGRE
ATLANTIC
OCEAN
93
dark, stormy sky. A law prohibits cutting these majestic trees, but once pasture is burnt around them, the Amazon
sun inevitably desiccates them.
Disagreements about extractive reserves pivot on questions of economic viability. Scientists on one side argue
that insucient markets exist for many
of the products. By studying past market cycles, Alfredo Kingo Oyama Homma of the Brazilian Enterprise for Agricultural Research ( EMBRAPA ) found
that when a forest product such as latex becomes commercially important
it is inevitably introduced into higheryielding plantations; in 1991 about 60
percent of Brazils natural rubber came
from plantations. Or the material is
made synthetically. As a result, the price
plummets, and small-scale extraction
ceases to be protable.
Other researchers counter that the
matter has not been settled. One study
conducted in Peru several years ago
found that 72 products could be harvested from a one-hectare plot for an
annual yield of $422. The investigators
concluded that this approach was more
lucrative than the one-time logging profit of $1,000. On the other hand, Anderson notes, if you took a random sample of forests here in the Amazon, you
would not nd many that would have
such a high value of nontimber forest
products. In addition, the Peruvian
products could be marketed regionally, a situation that does not yet exist
RUBBER TAPPER extracts latex . As the pattern of diagonal lines shows, tappers repeatedly cut each of the rubber trees on their land to collect the white liquid.
94
and then left. The investigations support one of the most exciting possibilities for sustainable development. If already deforested areas could be eciently used for agriculture, ranching or
logging, pressure could be taken o the
primary rain forest. There is no need
to deforest when two thirds of the already deforested land is not being used
in a reasonable way, Uhl notes.
Alternatively, if such lands could be
restored or coaxed back into forest,
biodiversity could be better protected.
Understanding which trees, plants and
creatures reestablish themselves rst
and under what conditions could allow researchers to speed up the recovery. Uhl cautions, however, that making
the process economically attractive is
95
SAWMILL NEAR PARAGOMINAS, a town in the eastern Amazon, is one of 238 in the vicinity. Although Brazil supplies less
than 5 percent of the worlds hardwood, this share is expect-
98
FURTHER READING
THE FATE OF THE FOREST: DEVELOPERS,
DESTROYERS AND DEFENDERS OF THE
AMAZON. Susanna Hecht and Alexander
Cockburn. HarperPerennial, 1990.
BIODIVERSITY. Edited by E. O. Wilson.
National Academy Press, 1992.
THE LAST NEW WORLD: THE CONQUEST
OF THE AMAZON FRONTIER. Mac Margolis. W. W. Norton and Company, 1992.
SUSTAINABLE AGRICULTURE AND THE ENVIRONMENT IN THE HUMID TROPICS. National Research Council. National Academy Press, 1993.
99
Antibody Anatomy
NATURAL ANTIBODIES
RADIOISOTOPE
JARED SCHNEIDMAN/JSD
MOUSE (MURINE)
ANTIBODY
CHIMERIC
ANTIBODY
ANTIBODY
FRAGMENT (Fab)
RADIOLABELED
ANTIBODY
GRAFTED
MURINE
BINDING
SITES
HUMAN
ANTIBODY
HUMANIZED
ANTIBODY
SINGLE-CHAIN
ANTIBODY
BI-SPECIFIC
ANTIBODY
101
Humanized Antibodies
Cytogen: Preclinical evaluation for breast, lung and ovarian cancer.
Genentech with NeoRx: Phase II for breast and ovarian cancer.
IDEC Pharmaceuticals: Preclinical testing of primatized macaque/
human antibody for rheumatoid arthritis.
Protein Design Labs: Phase II for graft versus host disease; phase I and
II for acute myeloid leukemia; preclinical tests for lung, colon and breast
cancer, inflammation, lupus and multiple sclerosis.
Human Antibodies
Protein Design Labs: Completed phase I and II for retinitis and hepatitis
B; preclinical tests for herpes and chicken pox.
*Marketing approval of drugs by the Food and Drug Administration generally requires three
phases of human clinical tests: the first for safety and toxicity, the second for efficacy on a
small scale and the final for large-scale, statistically significant effectiveness.
tact MAb will pass through the circulatory bed of a tumor many more times
than will a fragmented version.
Researchers at Scotgen and elsewhere
are also joining two dierent antibodies
to make X-shaped bi-specic antibodies that attach to a diseased cell on one
end and an immune cell on the other,
dragging immunologic soldiers to the enemy. Medarex recently began clinical trials on such a drug for breast and ovarian cancer. The problem is making these
things, Fildes complains. Its a long,
tortuous and very expensive process.
Indeed, all these new technologies are
considerably more expensive than churning out old-fashioned murine MAbs. And
there are no guarantees. Centocors human antisepsis monoclonal fared little
better than Xomas murine version in
nal ecacy trials. After investing $250
million in development, Centocor has
seen just $31 million in sales. McKearn,
for one, takes this as a sign that it is too
early to dismiss mouse monoclonals.
The literature is replete with examples
where people have ignored common
sense and simply jumped on the bandwagon of humanization, he says. But of
course sometimes the bandwagon goes
straight to the party. W. Wayt Gibbs
Earcons
Audification may add
a new dimension to computers
drian Parton used to spend his days pondering molecular biology. Then, in 1991, he heard a talk given
by biophysicist Ronald Pethig of the University College of
Wales, in which he described how electric fields can be
used to manipulate particles. That set Parton, who works
for Scientific Generics, a technology consulting firm in
Cambridge, England, thinking about rotating fields.
A rotating electric fieldeasily produced from four electrodescreates a torque on small particles that can make
them spin if the frequency is right. Parton has shown that
the effect can function as the basis for an extremely sensitive assay to detect microscopic parasites and even single biological molecules. Co-inventors Parton and Pethig
call it the electrorotation assay.
Scientific Generics has now embarked on a joint venture with Severn Trent, a water utility in England, to develop and license equipment based on the principle. One of
the first applications that will be pursued by the new company, Genera Technologies, is an apparatus to assess water-supply contamination by Cryptosporidium, a common
waterborne parasite that caused an outbreak of sickness
in Milwaukee, Wis., this past spring. Parton maintains that
the assay could reliably detect other small beasties as
well, such as Giardia, an intestinal parasite.
What is more, Parton says, the assay can outperform
ELISA (which stands for enzyme-linked immunosorbent assay), a widely used laboratory technique for detecting small
quantities of specific proteins. Genera plans to pursue several applications in the health care and food industries.
To detect Cryptosporidium, Parton first concentrates the
particulates from a 1,000-liter sample of water into two
103
a $147,000 grant from the National Science Foundation to work with an experimental psychologist on determining how well the ear can hear the subtle changes in pitch, loudness and other sound traits within an aural display.
You can arrange a clever scheme for
visualization and audication, but the
question is how will people perceive it,
Smith says.
Sound-display artists hope the ear will
in some situations surpass the eye
because of its superb ability to extract
meaning from a noisy environment.
Gregory Kramer of the Santa Fe Institute and W. Tecumseh Fitch of Brown
University found that a group of university students who were assigned to
role-play as medical doctors were able
tax policy to stimulate economic activity. The government has also dismissed as too expensive proposals
that it fund Faraday Centrestechnology-transfer institutes modeled on
the German Frauenhofer Institutes
to foster mixing among academic and
industrial scientists.
Rather Waldegrave sees a case for
improved direct support for strategic research in key areas, that is, work
somewhere between completely unfocused blue sky investigation and
product development. And he would
like to see a little more coordination
and a little more structured interchange between government, academia and industry.
There are misgivings about the applied focus of the governments re- WILLIAM WALDEGRAVE is presiding over
view in academic quarters. And the rst complete shake-up of British sciWaldegrave insists he can promise ence in nearly two decades.
no increases in support for civilian
research. The $1.7 billion planned for the 199394 fiscal year was intended to
be a modest boost, but scientific organizations argue that the devaluation of
the pound turned it into a decrease.
The budget strictures mean there is likely to be no quick relief for impoverished scientists. Pay is almost unbelievably low by U.S. standards. A trainee researcher relying on the Science and Engineering Research Council for support,
for example, has to survive the first three years after graduation on a stipend of
less than $7,000 a year, a third of the national average wage. The government
seems to have accepted the need for a remedy, and William D. P. Stewart, who is
the governments chief scientific adviser, is sympathetic to proposals to make
blue sky grants for young researchers easier to obtain. But, he warns, any increases in support for research will have to be coupled with demonstrated increases in efficiency.
Britain will be looking for ways to improve efficiency in international big science projects as well, says Stewart, who is a botanist. He declares that the
country cannot be party to the construction of expensive research facilities that
stem from national pride (a dig at the U.S.s Superconducting Super Collider).
Rather he favors planned international collaborations.
Increasingly, British scientists say they are willing to recognize the financial
realities of research, and some are even anxious to see their work commercialized. But dispelling the British economic malaise will be a tall order, even for a
scientific magic wand.
Tim Beardsley
Practical Fractal
Mandelbrots equations
compress digital images
107
tients rely on insurance, they will demand more treatment. Economic theory
suggests that forcing patients to cover a
percentage of their medical bills would
curb spending. But, as Henry J. Aaron
of the Brookings Institution observes, if
patients paid enough to make them really cost-conscious, a single bout of serious illness would spell nancial ruin
(as it does today for the uninsured).
Furthermore, Aaron points out, most
health care dollars are spent during episodes of acute illness, when patients
have little control over charges. Indeed,
in another example of perversity, conventional limits on out-of-pocket costs
may mean that patients have more nancial incentive to postpone a checkup than to avoid a major operation.
Health maintenance organizations
(HMOs), which oer to meet all of a
consumers medical needs for a xed
fee, have been cited as a major ingredi-
Ecient, competitive
health care markets may
be in the same class as
powdered unicorn horn.
ent in the managed competition plan.
But, as Reinhardt and others note, these
groups create a dierent and opposing
set of perverse incentives for physicians
and patients. Doctors receive a xed salary and so do best nancially by oering as little care as possible; patients
have paid up front and so prot (if that
is the right term) by insisting on maximum treatment. The HMO itself has an
incentive to sign up a maximum of subscribers and to minimize the time each
one spends with a physician.
Given this set of imperfect alternatives, critical economists say, the objective of health care reform must be to
downplay the inherent aws in this particular market rather than making futile
attempts to eliminate them. But is this
insight useful? Most of the suggestions
they oer are modications to the current status, not radical departures in the
vein of, say, Great Britain or Canada.
Reinhardt proposes reducing perverse
incentives by setting physicians incomes according to the number of pa-
109
MATHEMATICAL RECREATIONS
The Topological Dressmaker
HANDLE
HOLE
TUNNEL
by Ian Stewart
OUTSIDE
DRESS
INSIDE
SKIRT
SIDE
LINING
SKIN
SIDE
This conguration in turn is topologically equivalent to a twohandled torus with two holes, hems of dress and lining (right).
imagine sticking a nger into the tunnel and straightening it. Then the part
of the surface outside the tunnel is a
rather distorted handle, which can be tidied up to look like a neater one. Then
you got something that looked just like
a torus again [see illustration below].
6
7
8
111
TO TURN the ensemble inside out, reverse the whole thing. Pull the tunnels out to form
handles. Twist the handles into correct position. Note, however, where seams end up.
112
BOOK REVIEW
by Gerard Piel
114
EXTENSIVE SLUMS in Rio de Janeiro kept the 1992 United Nations Conference on
Environment and Development conscious of the worlds most serious problems.
( The photograph does not appear in the book under review.)
believe may occur around 2045, the population supertanker will have moved a
long way.
It must indeed make a dierence, as
Kennedy argues, whether human beings
stabilize their numbers at 10 billion or
20 billion. This, not the nightmare increase to terminal misery, is the population crisis.
The human presence already perturbs
the life cycles of the planetary ecosystem. The industrial revolution, by making all the citizens in some nations rich
and by lengthening the life expectancy
of people even in the poorest nations,
has amplied that inuence. In their different ways, the rich, by their appetites,
and the poor, in their increasing number, devastate the local, regional and global environment.
Kennedy gives rst priority to the
threat of global warming. (The evident
eects of the thinning of the ozone layer on photosynthesis may soon give that
threat higher priority.) Observation has
established a measurable increase in the
current concentration of carbon dioxide in the atmosphere; that is the result
principally of the fourfold increase since
1950 in the combustion of fossil fuels.
The geologic record shows the average
ambient global temperature rising and
falling in correlation with change in that
concentration. Whatever scientic uncertainty qualies the present threat,
almost equally hopeful but separate appraisal. Here he fails to reckon with the
reality of the Greater East Asia Co-Prosperity Sphere. The tigers and still bigger new partners, Indonesia, Malaysia
and Thailand, run huge decits in their
trade with Japan; they oset them by a
combined surplus in their trade with
the U.S. that is equal to Japans. Surely,
the future of this empire, now in such
good working order, strongly conditions
the future of each of its members, starting with Japan.
India and China, with one third of the
worlds people, command consideration
together. Population growth reduces
their impressive achievements in economic development to small per capita
gains, Indias smaller than Chinas. Equity in distribution of gains, more so in
China than in India, has advanced both
nations into the demographic transition,
again China ahead of India. Together
they are bound to make huge additions
to the ultimate world population and
still huger contributions to the concentration of carbon dioxide in the atmosphere. Economic change will put their
unity as nations under stress. For individual Indians and Chinese, life will be
hard but less brutish and short.
In assessment close to prophesy, Kennedy sees the calamity of Africa below
the Sahara extending without remission
into the 21st century. Second only to
that of Africa, the poverty of Latin America promises to resist whatever development its countries achieve. In this connection, Kennedy does not give enough
weight to the inequality, amounting to
inequity, in income distribution prevailing in the region: the top 20 percent income group in Brazil keeps 62.6 percent of the gross national product and
allots 2.4 percent of it to the bottom
20 percent.
Hardest to decipher, Kennedy decides,
are the futures of the erstwhile U.S.S.R.
and its former buer states in Eastern
Europe. Russia is bearing the brunt of
the Soviet triple crisisthe economic
incompetence of a lopsided industrial
system, the uncertain legitimacy of the
successor political powers and the rush
of ethnic minorities to self-determination. However it weathers the near term,
Russia faces the long-term ethnic revenge of population explosion in the
newly sovereign Siberian republics.
( They, as well as Kennedy, may call it
revenge, but they owe their population explosions to Russian promotion
of economic development in the Soviet
internal Third World.) Poland, the former Czechoslovakia and Hungary are
prospective fast adjusters, with economies recovering to 1989 levels as early
as next year. Even the slow adjusters
Romania and the Balkansget there
117
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118
U.N., at the very least an agenda for ongoing debate in the General Assembly.
Implementation of Agenda 21 relies,
of course, on the forthcoming of that
$125 billion a year. As Kennedy notes,
the Nordic countries (and Canada) are
laying out 0.7 percent of their GNP in
economic assistance to the developing
countries. They are only making good
on a promise in which all the industrial
countries joined 20 years ago. In 1961,
on a motion made by John F. Kennedy,
they had promised 1.0 percent of their
GNP to make the 1960s the Decade of
Development. When the 1960s went
into history as the decade of disappointment for the preindustrial countries, the
industrial countries committed to the
more realistic figure of 0.7 percent.
By no coincidence, that is precisely the
percentage of the GNP of the industrial
world that yields $125 billion. At Rio,
the rich countries, with the exception
of the U.S., promised to bring their outlays for economic assistance up to the
0.7 percent as soon as possible. The
European Community and Japan were
ready to make a down payment on their
promise. They refrained out of diplomatic courtesy to the Bush reelection
campaign and are waiting for the Clinton administration to settle into oce.
If Agenda 21 has been so little celebrated in the U.S. mass media as to
make this mention of it the rst that
has called it to the readers attention,
more will be heard of it during this last
decade of the 20th century. Agenda 21
now has its own undersecretary general for sustainable development installed
at U.N. headquarters in New York City
and a determined caucus of developing
countries in the General Assembly. It is
gathering the support, moreover, of the
citizen movements around the world
that put environmental protection agencies into nearly every national government during the past two decades. At
Rio, in their own Global Forum, 20,000
environmental zealots learned that poverty connects the integrity of the environment to development.
Anxious to create jobs, especially in
the smokestack industries, President Bill
Clinton may soon nd it desirable to
seek to increase the U.S. annual outlay to
foreign aid above the present paltry
and misdirected 0.2 percent of the countrys GNP. His vice president is on record advocating a global Marshall plan.
More sympathetic acquaintance with
the relevant political and economic realities, as well as with continuities of
human experience less familiar to him,
might have encouraged Paul Kennedy to
urge bolder action.
GERARD PIEL is chairman emeritus of
Scientic American.
ESSAY