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A French science colossus Sundance film picks Using ultrasound to monitor
faces a reckoning p. 1046 for scientists p. 1052 tissue health pp. 1058 & 1096

$15
8 MARCH 2024
science.org

TROUBLE
BELOW
Deepwater sharks threatened
by harvest p. 1135
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 CONTENTS

1052
8 M A R C H 2 0 24 • VO LU M E 3 8 3 • I S S U E 6 6 87

NEWS 1041 Gars truly are ‘living fossils,’ massive

DNA data set shows
The fish’s genomes change so slowly that
species separated since the dinosaurs can
IN BRIEF produce fertile hybrids today By A. Heidt
1036 News at a glance 1042 Brazil is hoping and waiting for
a new vaccine as dengue rages
IN DEPTH A locally produced vaccine did well in a phase
1038 U.S. giant telescopes imperiled 3 clinical trial but won’t be available until at
by funding limit least 2025 By M. Triunfol
NSF faces choice between multibillion-dollar
projects after board sets cost cap By D. Clery 1043 Final spending bills offer gloomy
outlook for science
1039 Surprise RNA paints colorful Congress makes sizable cuts at key funding
patterns on butterfly wings agencies By Science News Staff
Understudied means of
regulating genes is likely 1044 Skin side effects stymie advance
widespread in butterflies— of HIV vaccine
and perhaps other animals Strategy of using multiple mRNA shots to
By E. Pennisi hone powerful antibodies hits a pothole
By J. Cohen
1040 Smithsonian urged
to speed repatriation of FEATURES
human remains
INSIGHTS
BOOKS ET AL.
1052 Review roundup
Science at Sundance 2024
PERSPECTIVES
1057 Two rings to rule them all
A single photonic device accommodates
three different modes of operation
By A. Rolland and B. M. Heffernan
RESEARCH ARTICLE p. 1080
1058 Monitoring homeostasis
with ultrasound
An implant could allow at-home monitoring
of deep-tissue changes after surgery
By S. N. Sharma and Y. Lee
RESEARCH ARTICLE p. 1096
1059 Breathing control of vocalization

CREDITS: (ILLUSTRATION) HEDOF; (PHOTO) NICOLAS TUCAT/AFP VIA GETTY IMAGES

1046 The reckoning A crucial brainstem circuit for vocal-
Task force says Didier Raoult and his institute found respiratory coordination of the larynx is
museum should fame during the pandemic. Then, a revealed By S. R. Hage
return many of group of dogged critics exposed major RESEARCH ARTICLE p. 1074
its 30,000 ethical failings By C. O’Grady
remains and seek 1060 Amphibian hatchlings find
descendants’ consent b At the height of his fame, French
mother’s milk
for research microbiologist Didier Raoult inspired
Egg-laying amphibian females produce
By R. Pérez Ortega a nativity figurine. lipid-rich “milk” to feed offspring after
hatching By M. H. Wake
RESEARCH ARTICLE p. 1092

POLICY FORUM
1062 Accounting for the increasing
benefits from scarce ecosystems
As people get richer, and ecosystem services
scarcer, policy-relevant estimates of
ecosystem value must rise By M. A. Drupp et al.

1032 science.org SCIENCE

 LETTERS
1066 Reform wildlife trade in the
European Union By P. Cardoso et al.

1066 Incorporate ethics into US public

health plans By R. Anthony et al.

1067 Mangrove forest decline on Iran’s

Gulf coast By H. Yarahmadi and Z. Khorsandi

RESEARCH
IN BRIEF
1068 From Science and other journals

REVIEW
1071 Neuroscience
Structure, biophysics, and circuit function of
1111
a “giant” cortical presynaptic terminal The bacterium Wolbachia blocks sperm development in the primary spermatocytes of its insect host
D. Vandael and P. Jonas by targeting a long noncoding RNA (shown in cyan in this fluorescence confocal image; nuclei are yellow).
REVIEW SUMMARY; FOR FULL TEXT:
DOI.ORG/10.1126/SCIENCE.ADG6757

1092 Life history 1135 Conservation

RESEARCH ARTICLES Milk provisioning in oviparous caecilian Fishing for oil and meat drives irreversible
1072 Adult stem cells amphibians P. L. Mailho-Fontana et al. defaunation of deepwater sharks and rays
Vitamin A resolves lineage plasticity to PERSPECTIVE p. 1060 B. Finucci et al.
orchestrate stem cell lineage choices
M. T. Tierney et al. 1096 Biomedicine 1142 Quantum imaging
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT: Bioresorbable shape-adaptive structures Adaptive optical imaging with entangled
DOI.ORG/10.1126/SCIENCE.ADI7342 for ultrasonic monitoring of deep-tissue photons P. Cameron et al.
PODCAST homeostasis J. Liu et al.
PERSPECTIVE p. 1058
1073 Plant science DEPARTMENTS
Enhancing rice panicle branching and grain 1104 HIV 1035 Editorial
yield through tissue-specific brassinosteroid Induction of durable remission by dual Collections are truly priceless By C. C. Davis
inhibition X. Zhang et al. immunotherapy in SHIV-infected
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT: ART-suppressed macaques S.-Y. Lim et al.
DOI.ORG/10.1126/SCIENCE.ADK8838
1150 Working Life
Writing my ticket By V. J. Rodriguez
1111 Symbiosis
1074 Neuroscience
Prophage proteins alter long noncoding
Brainstem control of vocalization and its
RNA and DNA of developing sperm ON THE COVER
coordination with respiration J. Park et al.
to induce a paternal-effect lethality Rough sharks (Oxynotidae) are a small family
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT:
DOI.ORG/10.1126/SCIENCE.ADI8081
R. Kaur et al. of deepwater sharks consisting of five species.
PERSPECTIVE p. 1059 Three species are threatened with extinction from
1118 Attosecond science overfishing. Their slow growth and few young,
1075 Geology Attosecond-pump attosecond-probe combined with an unusual
CO2 drawdown from weathering is maximized x-ray spectroscopy of liquid water diet of shark eggs, make
at moderate erosion rates A. Bufe et al. S. Li et al. this group of deepwater
sharks susceptible to over-
1080 Photonics 1122 Cell biology fishing, which highlights the
PHOTO: RUPINDER KAUR/PENNSYLVANIA STATE UNIVERSITY

Sister chromatid cohesion is mediated by need to provide refuge from

Multimodality integrated microresonators
human activities. See page
using the Moiré speedup effect Q.-X. Ji et al. individual cohesin complexes F. Ochs et al.
1135. Photo: Jordi Chias/
PERSPECTIVE p. 1057
NPL/Minden Pictures
1130 Paleoecology
1084 Neuroscience Climate change is an important predictor
Axonal self-sorting without target guidance in of extinction risk on macroevolutionary Science Staff ............................................1034
Drosophila visual map formation E. Agi et al. timescales C. M. Malanoski et al. Science Careers ........................................1149

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SCIENCE science.org 8 MARCH 2024 • VOL 383 ISSUE 6687 1033

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1034 8 MARCH 2024 • VOL 383 ISSUE 6687 science.org SCIENCE

 EDITO RIAL
Collections are truly priceless
L
ast month, Duke University in North Carolina an-
nounced that it was shuttering its herbarium. The
collection consists of nearly 1 million specimens
representing the most comprehensive and his-
toric set of plants from the southeastern United
States. It also includes extensive holdings from
other regions of the world, especially Mexico,
Central America, and the West Indies. Duke plans to
disperse these samples to other institutions for use or
storage over the next 2 to 3 years, but this decision re-
flects a lack of awareness by academia that such col-
lections are being leveraged as never before. With
modern technologies spanning multiple fields of study,
the holdings in herbaria and other natural history col-
lections are not only facilitating a deeper and broader
understanding of the past and pres-
ent world but are also providing tools
to meet both known and unforeseen
challenges facing humanity. Science
and society can hardly risk the loss of
“…society can
such an important resource.
Sadly, Duke is not the first world-
hardly risk the
class institution to withdraw support
from, and cease the operation of, its
loss of such
natural history collections. In the
late 1970s and early 1980s, Prince-
an important
ton and Stanford Universities did
the same. Ostensibly, the decisions to resource.”
close those collections were made to
shift priority to research programs in
molecular biology and biochemistry, which were con-
sidered closer to science’s cutting edge of discovery
and able to attract more external funding. Ironically,
nearly half a century on, biological sciences depart-
ments at these institutions and comparable ones in
China, Brazil, some regions in Africa, and in most
of Western Europe are filled with world-class schol-
ars who—knowingly or unknowingly—use herbaria,
zoological collections, and their derivatives every day
for transformative research published in the highest-
impact journals.
Herbaria have long been a critical resource for eco-
logical and evolutionary research but have recently be-
come relevant to many more fields, including climate
science, anthropology, genetics, computer science,
chemistry, and medicine. Specimens are being mobi-
PHOTO: KRIS SNIBBE/HARVARD UNIVERSITY
lized to investigate plant–animal and plant–pathogen
interactions, crop domestication, compounds with po-
tential applications in agriculture and pharmaceutics,
and human migration over time and space. Advances in
genome sequencing and machine learning are guiding
SCIENCE science.org
biodiversity monitoring efforts and revealing knowl-
edge gaps where specimen sampling is needed.
The decision by Duke comes at a time when wide-
spread awareness of and access to herbaria are growing
in tandem. This is principally a result of the large-scale
digitization of natural history collections, an endeavor
that has been extensively supported by governmental
agencies and philanthropic organizations worldwide. Charles C. Davis
This innovation is arguably one of the greatest trans-
is a professor in
formations in biodiversity science since DNA sequenc-
the Department
ing. In short, creation of the Global Metaherbarium—an
of Organismic
open-access, global interlinked virtual resource—makes
physical herbaria discoverable and is attracting new in- and Evolutionary
terest in the utility of these collections for sophisticated Biology, and
multiomic investigations (genomics, transcriptomics, Curator of Vascular
metabolomics, proteomics, and mi- Plants, Harvard
crobiomics) and for research that con- University Herbaria,
nects science with the broader society. Cambridge, MA,
Closure of the Duke Herbarium
also points to changes needed in for-
USA. cdavis@oeb.
harvard.edu
mally recognizing herbaria and other
natural history collections in research
initiatives and agendas. Collections in-
creasingly have become the first line
of genetic and genomic sampling for
investigators who otherwise eschew
conventional field work. Requests to
destructively sample specimens are
often central to rapidly expanding big
data initiatives. These requests place
enormous demands on the institutions and staff who
support collections but who largely go unrecognized for
their crucial work. In turn, users of these collections,
many of whom are not based at these institutions,
benefit from grants and high-profile papers in which
herbaria are only briefly acknowledged, if they are men-
tioned at all. Scientists who oversee collections should
be fully funded partners in research initiatives. Insti-
tutions, herbarium curators, and support staff should
be coauthors of studies, with contributions indicated
through the Contributor Roles Taxonomy (CRediT)
system, for example. Such recognition could help more
directly measure the impact and influence of natural
history collections on scholarly research.
Universities should support the priceless resources
and heritage represented in natural history collections.
They also should have the vision to provide for, and
commit to, the long-term stewardship and robust intel-
lectual environment for open inquiry and deep research
that these collections provide across generations.
–Charles C. Davis
10.1126/science.ado9732
8 MARCH 2024 • VOL 383 ISSUE 6687 1035
 NEWS 650%
Increase since 2009 in the share price of scientific publishing giant Elsevier’s
parent company RELX and its predecessor. The stock is the top performer
on the U.K.’s FTSE 100 index in its 40-year history. In 2023, RELX’s scientific
division reaped a profit margin of 38%. (Financial Times, RELX annual report)

IN BRIEF U.S. deports Chinese students

Edited by Jeffrey Brainard
SECURITY | An unusual town hall last week
at Yale University highlighted a recent
spate of incidents in which immigration
authorities blocked Chinese graduate
students from returning to U.S. universities
after visiting family in China. More than a
dozen students in Ph.D. science programs
at Yale, John Hopkins University, and
other major U.S. research institutions had
their visas revoked and were immediately
sent back home. U.S. Customs and Border
Protection (CBP) declined to discuss spe-
cific cases. Immigration lawyers suspect
the influence of a 2020 presidential direc-
tive that gives CBP agents the authority to
deny entry to Chinese graduate students
and postdocs who have received support
from entities suspected of stealing U.S.
technology. Yale’s graduate school of arts
and sciences hosted the 26 February event
for its international students, who make up
nearly half the school’s enrollment.

A 1953 nuclear test in Nevada was among the human activities that could have marked the Anthropocene.
Methane satellite begins work
| The Environmental
C L I M AT E S C I E N C E
Defense Fund (EDF) this week became the
STRATIGRAPHY first nonprofit group to launch a satel-
lite to track methane emission sources.
Anthropocene epoch gets voted down MethaneSAT, funded by EDF donors, is
designed to detect methane emissions in

A
group of two dozen geologists has turned down a proposal to high resolution above known oil-and-gas
classify the Anthropocene as an “epoch” that would mark human- facilities, filling a gap in coverage. Its data
will support efforts to regulate and reduce
ity’s overwhelming influence on the planet, a tally released this
leaks and other sources of the potent
week indicates. For 15 years, researchers had considered desig- greenhouse gas. The group plans to pro-
nating this formal unit of geologic time, and in 2023 they chose a vide the data for free, in nearly real time,
marker of when it started, a layered sediment core from Canada’s at www.MethaneSAT.org.
Crawford Lake that shows a global acceleration in carbon dioxide emis-
sions and atmospheric nuclear weapons testing during the 1950s. But U.K. funder clears diversity panel
PHOTO: NNSA/NEVADA FIELD OFFICE/SCIENCE SOURCE

over the past month, the proposal failed to win a supermajority of votes POLITICS | The United Kingdom’s national
from a panel of the International Commission on Stratigraphy, with funding agency has reinstated its advisory
some members stating that the proposed start date failed to account panel on diversity, equity, and inclusion,
which was suspended in October 2023
for earlier human influences. Barring an unexpected reversal, the for- after science minister Michelle Donelan
mal classification cannot be reconsidered for another decade. But even said members of the newly created panel
opponents of the proposal acknowledge humanity’s potent, transfor- had posted “extremist” views on social
mative effects on Earth and the power of the term Anthropocene, and media about the Israel-Hamas conflict.
This week, UK Research and Innovation
some suggest considering it, like some other great changes in the plan- (UKRI) reported the results of its investiga-
et’s history, a geologic “event”—a usage that requires no formal ratifica- tion into the matter, concluding that the
tion or exact start date. panel members had not violated a code

1036 8 MARCH 2024 • VOL 383 ISSUE 6687 science.org SCIENCE

 NATURAL HISTORY

Scanning project creates huge digital menagerie

B
iologists have completed a free, online repository contain-
ing x-ray scans of vertebrate specimens from 16 museum
collections across the United States. The openVertebrate
collection, one of the largest of its kind, covers more than
13,000 specimens, including more than half the genera
of amphibians, reptiles, fishes, and mammals. Led by the Florida
Museum of Natural History, researchers spent 5 years making
computer tomography scans and creating 3D reconstructions;
most show only the animals’ skeletons, but some samples were
stained before being scanned to reveal internal organs. As of
December 2023, the database had received more than 1 million
views and nearly 100,000 downloads. The digital collection has
already led to new research findings, including unusual bones in
African spiny mice (pictured, with tail colored red) and evidence
that frogs have lost and regained teeth more than 20 times
during their evolution. Project organizers also trained secondary
school teachers to use the images for science education. The
project’s impact is described in the 6 March issue of BioScience.

of conduct for public servants or posted
problematic views. Although Donelan had
asked UKRI to shut down the diversity
panel, UKRI’s statement said the inves-
tigation concluded the panel’s work is
necessary, and it will reconvene. Separately,
a lawyer for a panel member, Heriot-Watt
University gender studies professor Kate
Sang, announced on 5 March that Donelan
had agreed to pay Sang an undisclosed
settlement and retract her “false” state-
ment about Sang’s social media post.
Trustees protect Kinsey Institute
POLITICS | The Kinsey Institute, the famed
research center on human sexuality, will
remain part of Indiana University (IU),
despite a 2023 state law that blocks the
institute from receiving taxpayer dollars.
IMAGE: OPENVERTEBRATE
the institute is funded only by nonstate
sources, including its own endow-
ment and the university’s foundation.
A proposal floated earlier would have
created a new nonprofit organization to
fund and manage some of the institute’s
administrative functions while allow-
ing its faculty and collections to remain
within the university. But some research-
ers worried the split would expose the
institute to future legislative crackdowns,
The Guardian reported.
Finding new uses for drugs
C L I N I CA L R E S E A R C H | A nonprofit that
seeks to repurpose approved drugs for
new indications will receive more than
$48 million from the U.S. Advanced
Research Projects Agency for Health to
Philadelphia-based nonprofit was co-
founded by University of Pennsylvania
immunologist David Fajgenbaum, who
a decade ago identified a treatment—
sirolimus, which prevents organ
rejection—for his own rare, life-threaten-
ing immune condition, Castleman disease.
Pesticide database restored
| The U.S. Geological
AG R I C U LT U R E
Survey (USGS) has backtracked on cuts to
a widely used database of approximately
400 agricultural pesticides after pleas
from scientists. The agency had reduced
the number of compounds tracked in
2019 by the Pesticide National Synthesis
Project, which documents estimated
annual application rates, from 400 to 72,
citing budget constraints. Then last year,

Conservative lawmakers targeted the
institute after one claimed its research
promotes sexual abuse, an allega-
tion Kinsey’s defenders call baseless.
Last week, IU’s board of trustees voted
unanimously to develop a plan ensuring
supercharge its work, the agency said
on 28 February. Every Cure plans to
use artificial intelligence to predict the
power of more than 3000 approved drugs
against more than 10,000 rare diseases,
most without effective treatments. The
USGS halted the annual release of pre-
liminary data, opting instead to publish
final data every 5 years. Last week, the
agency said it will restore the database’s
pre-2019 scope, and data for 2018 to 2022
will be published in 2025.

SCIENCE science.org 8 MARCH 2024 • VOL 383 ISSUE 6687 1037

NE WS
The Thirty Meter Telescope (artist’s
conception) in Hawaii is one of two
projects seeking public funding.
IN DEP TH
ASTRONOMY
U.S. giant telescopes imperiled by funding limit
NSF faces choice between multibillion-dollar projects after board sets cost cap
By Daniel Clery
F
or several years, U.S. astronomers have
hoped the government would help build
a pair of giant ground-based telescopes.
But the National Science Board (NSB),
the panel of scientists that oversees the
National Science Foundation (NSF),
says the field can only afford one. At a meet-
ing on 22 February, NSB capped the budget of
the U.S. Extremely Large Telescope Program
(US-ELTP) at $1.6 billion and gave the agency
until May to come up with a process to choose
one of the two 30-meter class telescopes.
With a rival European telescope rapidly
taking shape on a mountaintop in Chile, the
NSB decision is a relief to those who want
U.S. astronomy to unite behind a realistic
plan and catch up. “I think the decision
was long overdue,” says John Monnier of
the University of Michigan. But for Richard
Ellis of University College London, “It’s a
tragedy, given the investment made in both
telescopes.” He adds, “There were many op-
portunities to merge or down select. Now,
the U.S. has lost a couple of years trying
to keep up with the European Southern
Observatory.”
Such giant telescopes are the next logical
step for cutting-edge astronomy. They will
allow researchers to zoom in on habitable
planets outside the Solar System and study
the formation of the first stars and galax-
ies. Today’s top telescopes, with apertures of
1038 8 MARCH 2024 • VOL 383 ISSUE 6687
8 to 10 meters, showed that many segmented
mirrors or several large ones could be com-
bined into a much larger effective mirror.
They also demonstrated adaptive optics: us-
ing rapidly deformable secondary mirrors to
cancel out the distortions caused by Earth’s
atmosphere to capture images as sharp as
those taken from space.
These technical advances spawned the two
U.S.-led projects: the Giant Magellan Tele-
scope (GMT) in Chile and the Thirty Meter
Telescope (TMT) in Hawaii. Both are backed
by consortia of universities, philanthropic
foundations, and international partners. But
this privately funded approach, which during
the 20th century produced groundbreaking
instruments, stumbled when it came to
multibillion-dollar projects. Although design
work and mirror casting forged ahead, both
The Giant Magellan Telescope, under construction
in Chile, is a smaller and cheaper project.
projects failed to amass enough funding.
So, in 2018 the projects, historically ri-
vals, joined forces as US-ELTP and made
an offer to NSF. In return for public fund-
ing, all U.S. astronomers would have access
to the telescopes, which would open un-
precedented views of the night sky above both
hemispheres, something Europe’s Extremely
Large Telescope (ELT) will not offer (Science,
25 May 2018, p. 839). The 2020 decadal sur-
vey in astrophysics, which defines the field’s
priorities for funders and Congress, put US-
ELTP first among ground-based projects, in
line with the recommendation of a panel led
by Timothy Heckman of Johns Hopkins Uni-
versity. “We felt this made a compelling case,”
IMAGES: (TOP TO BOTTOM) TMT INTERNATIONAL OBSERVATORY; GMTO CORPORATION
Heckman says. The NSB decision, he says, “is
a bittersweet outcome.”
NSF carried out preliminary design re-
views of both telescopes and approved them
in early 2023, but the costs are in a different
league from what NSF is used to. The GMT
is estimated to cost $2.54 billion, of which
existing partners have pledged $850 mil-
lion. The TMT’s partners have so far offered
$2 billion of its $3.6 billion price tag. In a
statement, NSB acknowledged the ambition
of the US-ELTP proposal but noted it would
soak up 80% of NSF’s entire funding for ma-
jor projects.
In an editorial in Science in November
2023, Michael Turner, an astrophysicist at
the University of Chicago, argued that insist-
ing NSF fund two telescopes put both proj-
science.org SCIENCE

ects at risk. NSF says it will have more to say
in the coming months on how it will choose
between the TMT and the GMT. “Neither is a
slam dunk. Both have risks,” Turner says. “I
don’t envy the NSF.”
Made up of 492 segments, the TMT’s
30-meter mirror makes for the larger, more
sharp-eyed instrument. But its chosen site,
the summit of Mauna Kea on Hawaii’s Big
Island, is opposed by some Native Hawai-
ian groups who consider the summit sacred.
They have blocked any construction work
since 2015. TMT officials hope work will be
able to proceed under the aegis of a new
state-appointed authority that governs the
mountaintop and includes both astronomers
and Native Hawaiians. “We’re working on our
relationships in Hawaii,” says TMT Executive
Director Robert Kirshner. “We’re learning
how to do that in a humble and straight-
forward way.” Turner says the impasse may
not be solved anytime soon. “I’m sure a so-
lution will be found, but it may take longer
than people like,” he says.
The GMT, smaller and cheaper, is a lower
risk choice. Its foundations are being laid on
a mountaintop at Las Campanas in Chile,
while support structures for its mirrors are
taking shape in the United States. Three of its
seven 8.4-meter mirrors, the equivalent of a
25.4-meter-wide mirror, are already finished;
the other four are being polished.
Because of the risks attached to the TMT,
Monnier and Ellis suspect NSF will prob-
ably back the GMT. But with a mirror less
than 40% of the size of its 39-meter Euro-
pean rival, the GMT “is no match for ELT,”
says Ellis, a former TMT board member.
Monnier thinks the GMT will probably be
good enough in key astronomy areas, but
NSF will need to judge whether those areas
are important for U.S. astronomers.
Abandoning either of these very capable
telescopes will harm U.S. astronomy, says
Wendy Freedman at Chicago, one of the
GMT’s partner organizations. “The science
that will come out really does justify two tele-
scopes.” Upcoming survey telescopes such as
the 8.4-meter Vera C. Rubin Observatory in
Chile will identify a wealth of interesting ob-
jects in need of follow-up observations by in-
struments on the GMT and the TMT that can
split the light into information-rich spectra.
“That’s what these big telescopes give you,”
she says.
Language in a spending bill passed by Con-
gress this week “strongly encourages” NSB to
build both telescopes, even though lawmak-
ers cut NSF’s 2024 funding by more than
PHOTO: LUCA LIVRAGHI
$800 million, to $9 billion (see story, p. 1043).
Freedman hopes the congressional direction
will prompt a rethink. “The United States will
sit out the future of astronomy if we don’t get
these telescopes,” she says. j
SCIENCE science.org
NEWS
BIOLOGY
Surprise RNA paints colorful
patterns on butterfly wings
Understudied means of regulating genes is likely
widespread in butterflies—and perhaps other animals
By Elizabeth Pennisi being sold on eBay. When they sequenced
dozens of these so-called ivory mutants,
A
mutant butterfly for sale on eBay they found a deletion in the region of the
has helped upend naturalists’ pic- cortex gene. They then realized the miss-
ture of how butterfly wings acquire ing DNA included a sequence encoding an
their intricate variety of red, yellow, lncRNA that no one had ever closely exam-
white, and black stripes. It and re- ined. Working with painted lady butter-
cent research into other butterflies flies (Vanessa cardui), which have colorful
show how visible traits in many animals wings and are easy to breed in the lab, they
may be controlled by an underexplored ge- used the gene editor CRISPR to disable just
netic regulatory mechanism, based not on the lncRNA’s gene. The edit yielded white-
proteins, but on RNA. winged painted ladies, just like the ivory
In 2016, geneticists thought they had Heliconius, they reported on 12 February
pinned much of the wing-pattern variation in a preprint on bioRxiv. Disabling cortex
on a protein-encoding gene called cortex. But had no effect.
three teams have now proved that a different Moreover, Livraghi’s team found this
gene, previously missed because it overlaps same lncRNA also controls black and other
with cortex, is the key. Its
final product is not pro-
tein, but RNA that regu-
lates genes responsible
for the pigmentation pat-
terns of black and other
hues on the wings. One
team also showed the
RNA is broken down into
a smaller RNA that fine-
tunes the production of
the colors. “They solved
a puzzle that had left
everyone in the com-
munity wondering,” says
Nicolas Gompel, a devel-
opmental biologist at the
University of Bonn.
The discovery, de- A gene edit affecting one wing (right) of this Heliconius erato radically
tailed in three preprints changed its normal color pattern.
this month, also rep-
resents the first time long noncoding RNA pigmentation in the scales of other butter-
(lncRNA), so-called because it does not code fly species, some distantly related. “We have
for proteins, has been linked to the evolution to conclude now that the key regulator is
of a visible trait in animals. “Now we have to an RNA, not a protein,” says Peter Holland,
pay more attention to noncoding RNA,” says an evolutionary biologist at the University
Ilik Saccheri, an evolutionary biologist at the of Oxford who was not part of any of the
University of Liverpool and a member of one new work.
of the teams that had focused on cortex. At a conference midway through these
For evolutionary developmental bio- studies, Livraghi learned that a Cornell Uni-
logist Luca Livraghi, now at George Wash- versity group studying wing color patterns
ington University, the key break came when in the buckeye butterfly (Junonia coenia),
a colleague told him and Joseph Hanly, a common throughout North America, was
bioinformatician at Duke University, about homing in on this same lncRNA. The two
completely white Heliconius butterflies teams decided to coordinate their efforts.
8 MARCH 2024 • VOL 383 ISSUE 6687 1039
NE WS | I N D E P T H
Come fall, especially in the U.S. East, the
light brown wings of buckeyes darken to
a deep red, enabling them to absorb heat
more efficiently. When Cornell evolution-
ary biologists Robert Reed and Richard
Fandino used CRISPR to knock out differ-
ent parts of the lncRNA in these butter-
flies, they were born with little or no color
and their fall reddening was altered, the
team reported on 19 February on bioRxiv.
A white butterfly mutant posted on the
social media platform X (formerly Twit-
ter) alerted Livraghi to the team behind
the third new preprint: evolutionary de-
velopmental biologists Antónia Monteiro
and Shen Tian at the National University
of Singapore. They were focused on short
RNA sequences, microRNAs, known to reg-
ulate gene activity in plants, animals, and
other eukaryotes—organisms that pack
their DNA in a nucleus. In the squinting
bush brown butterfly (Bicyclus anynana),
a well-studied tropical species, they found
that a microRNA was active in the black
wing pattern, just as Livraghi had found
for the ivory lncRNA.
When the Singapore team disabled the
DNA encoding this microRNA, mir-193,
bush brown wings became lighter, the
team reported on 12 February in a bioRxiv
preprint. Knocking out mir-193 also had
dramatic effects in a distant relative, the
Indian cabbage white (Pieris canidia),
changing its black-patterned wings to
completely white. After learning about
the lncRNA identified by the two other
groups, Monteiro and Tian concluded that
the longer RNA is broken down to produce
these microRNA.
“A lot is happening within this small part
of the genome,” says Violaine Llaurens,
an evolutionary biologist at the College of
France. She cautions that other regulatory
elements probably play a role in butterfly
wing patterns. But the fact that the same
microRNA fine-tunes coloration in very
distantly related species is “amazing,”
says Anyi Mazo-Vargas, an evolutionary
bio-logist at Duke who worked with Reed.
She suspects similar RNAs color wings in
most, if not all, of the 180,000 species of
moths and butterflies. And because mir-193
is conserved across the animal kingdom,
Monteiro and Tian think noninsects may
also make use of these regulatory RNAs.
Small RNAs derived from parent
lncRNAs affect traits in plants, too, says
Yaowu Yuan, an evolutionary biologist at
the University of Connecticut whose team
last year reported that so-called siRNAs
determine color in monkeyflowers. The
RNA realm is expanding, Yuan says. “I
am quite positive that many more similar
studies will come soon.” j
1040 8 MARCH 2024 • VOL 383 ISSUE 6687
MUSEUM COLLECTIONS
Smithsonian urged to speed
repatriation of human remains
Task force says museum should return many of its 30,000
remains and seek descendants’ consent for research
By Rodrigo Pérez Ortega first for the Smithsonian. It advises that no
research should be done without consent
S
ince the 19th century, scientists at from the deceased or their descendants.
the Smithsonian Institution have Research would be permitted without
obtained, studied, and stored more consent on ancient remains that cannot
than 30,000 human remains, one of be linked to any of today’s communities,
the largest such collections in the which are a small percentage of the total.
United States. In the past, many re- Other new recommendations in-
mains were studied in order to justify sci- clude returning as many remains as pos-
entific racism. Now, the institution should sible by 2030 and barring destructive
rapidly offer to return most of these re- sampling—to analyze DNA, for example—to
mains to lineal descendants or descen- identify descendants.
dant communities, according to a report Studies of the remains, such as DNA anal-
released last month by an institutional ysis of dental calculus to study pathogens,
task force. might be harder to carry out under the new
“It’s important to face this past and try to recommendations. Although there’s no of-
repair the harms caused by our institution ficial moratorium, no new human remains
and so many others,” says Sabrina Sholts, research has been approved in recent years
curator of biological because of stricter re-
anthropology at the Smith- quirements, Sholts says.
sonian’s National Museum “This first step towards She expects a pause on
of Natural History and approvals while the new
member of the task force. a long-overdue reckoning policy is established, but
Most of the Smithson-
ian’s human remains were
makes it more likely notes the report antici-
pates positive outcomes
collected without proper others will do the same.” from future research.
consent in the early The 15-member task
Sabrina Sholts,
20th century, and many force, including both
National Museum of Natural History
acquisitions were part Smithsonian staff and
of an attempt to prove outsiders, says the insti-
now-debunked notions of white superior- tution should ramp up its efforts to identify
ity. “It’s a collection that should have never both lineal descendants and communities
been amassed, and we’re committed to dis- of descent and then initiate contact, rather
mantling as much of it as possible,” wrote than waiting for repatriation requests. The
Secretary of the Smithsonian Lonnie Bunch report recommends the Smithsonian re-
III last year in an editorial. quest new funds and staff for the massive
The Smithsonian already has a process repatriation effort, but does not say how
for repatriating its 15,000 Native American much would be needed.
remains, as a 1989 federal law requires; it “I’m impressed,” says Carlina de la Cova,
has returned more than 5000. Now, the a biological anthropologist at the Univer-
report urges that the collection’s Indig- sity of South Carolina who is not on the
enous remains be returned more quickly task force. The recommendations “will
and that the effort extend to all human re- force scholars working with the dead to
mains. It also suggests prioritizing the re- think about how they engage with [re-
mains of other marginalized groups, such mains] and what that means for the living.”
as the collection’s 2100 African American She adds that it’s the first time a museum
remains, as well as the nearly 6000 re- has made such recommendations public,
mains of people whose names are at least and she expects other institutions to fol-
partially known. low the Smithsonian’s steps.
The task force applies a bedrock princi- Sholts agrees: “This first step towards
ple of research on living humans—the need a long-overdue reckoning makes it more
for informed consent—to the remains, a likely that others will do the same.” j
science.org SCIENCE

EVOLUTION
Gars truly are ‘living fossils,’
massive DNA data set shows
The fish’s genomes change so slowly that species separated
since the dinosaurs can produce fertile hybrids today
By Amanda Heidt
I
n 1859 Charles Darwin coined the term
“living fossil” to describe lineages that
have looked the same for tens of millions
of years, such as the coelacanth, sturgeon,
and horseshoe crab. The term captured
the popular imagination, but scientists
have struggled to understand whether such
species just resemble their long-ago ances-
tors or have truly evolved little over the eons.
Now, in a study published this week in Evo-
lution, researchers confirm that in some—but
not all—living fossils, evolution is at a virtual
standstill. The most striking examples are
prehistoric-looking fish called gars, which
have the slowest rate of molecular evolution
of all jawed vertebrates. The team also pro-
poses a mechanism to explain gars’ timeless-
ness: superb DNA repair machinery. That
repair has likely kept gar genomes so stable
that species whose last common ancestor
lived more than 100 million years ago have
diverged very little, and some can still hybrid-
ize today to produce viable offspring.
“That’s amazing,” says Tetsuya Nakamura,
an evolutionary developmental biologist at
Rutgers University. “This paper has a lot of
interesting work into this question of what
makes a living fossil, but when I read that, I
was shocked.”
PHOTO: SOLOMON DAVID
To see whether several putative living fos-
sils evolve more slowly than other vertebrate
groups, the team gathered published se-
quences from more than 1100 exons (the cod-
ing regions of the genome) across 478 species.
SCIENCE science.org
Using existing family trees for each group,
they created a massive evolutionary tree. For
each lineage, the researchers estimated the
rate at which each DNA base changed over
time—the so-called substitution rate.
Surprisingly, they found evolution was
not on pause in all living fossils. The coel-
acanth, the elephant shark, and a bird called
the hoatzin—all considered ancient—have
faster than expected mutation rates of about
0.0005 mutations at each site per million
years, although that was still slower than the
average rate for amphibians (0.007 mutations
per million years) and placental mammals
(0.02 mutations per million years). The find-
ings support the idea that some species that
still resemble their ancient ancestors have
nevertheless changed at a molecular level.
But gars, big freshwater fish with long,
toothy snouts, were different: In almost every
exon, gars had the slowest rates of molecular
substitution, often by several orders of mag-
nitude; they averaged only 0.00009 muta-
tions per million years at each site. Indeed,
two genera that diverged roughly 20 million
years ago had identical sequences at nearly
all the sites analyzed—a finding the team at
first attributed to sequencing error. “I came
into this project cautious about using the
term living fossil,” says study co-author Chase
Brownstein, an evolutionary biology Ph.D.
student at Yale University. “But for gars at
least, it’s an appropriate term.”
The authors posit that because gar mu-
tation rates seem consistently low across
sites—including in genomic regions un-
This fish is the hybrid offspring of an alligator gar and
a spotted gar—members of genera that last shared a
common ancestor at least 100 million years ago.
likely to be under selective pressure to stay
the same—a global mechanism likely drives
the slow substitution. They suggest gars
are extremely efficient at repairing DNA
after mutations or damage, keeping the
animals from evolving even as the conti-
nents have shifted around them. A similar
hypothesis has previously been proposed by
other researchers for sturgeon, which had
the second-lowest substitution rates among
vertebrates in the study.
DNA repair is “a reasonable hypothesis,
but there’s probably more than just one ex-
planation,” says Elise Parey, an evolutionary
genomicist at University College London.
For example, gars have slow metabolic rates
and long generation times, features that
could reduce mutation rates. Gars have also
preserved the arrangement of DNA in their
chromosomes and dampened the effects of
so-called jumping genes that can cause ge-
netic reshuffling as they move from place to
place in the genome. “This goes not just to
sequence changes, but also to chromosome
evolution, which would be an interesting av-
enue to explore,” Parey says.
To test their findings, the authors followed
up on reports of unusual gars that might
be natural hybrids in rivers throughout
Oklahoma and Texas. They analyzed tissue
samples from dozens of these fish to trace
their ancestry, finding that two gar genera—
Atractosteus and Lepisosteus—are crossing to
produce fertile, hybrid young. These groups
last shared a common ancestor roughly
105 million years ago, a record separation
time for eukaryotes that can produce viable
offspring. The gars beat the previous re-
cord holders—two species of fern—by about
60 million years. (Keen minds may re-
call reports of the sturddlefish, a hybrid of
paddlefish and sturgeon, which diverged
even longer ago, but those accidental hybrids
were likely sterile and don’t occur naturally.)
A next step will be to prove that gars’ DNA
repair mechanisms are indeed slowing their
genetic change. By equipping zebrafish—a
standard model animal—with gar DNA repair
genes, investigators might be able to observe
the genes at work. “This will be a challeng-
ing experiment though, because [DNA repair
genes] are fundamental,” Nakamura says.
But the authors say understanding how
gars keep their mutation rate so low could
have additional payoffs. For example, such
insights might help humans better under-
stand our own DNA repair pathways, which
can lead to cancer when they fail. j
Amanda Heidt is a science journalist in Utah.
8 MARCH 2024 • VOL 383 ISSUE 6687 1041
 Children are vaccinated against dengue at a health
center in Brasília, Brazil, on 9 February.

Rafael Mello Galliez, an infectious diseases

researcher at the Federal University of Rio
de Janeiro. Poor populations lacking run-
ning water and proper waste disposal bear
the brunt of the disease.
Regularly removing water reservoirs can
help control dengue—along with Zika and
chikungunya, two other viral diseases trans-
mitted by A. aegypti—but is hard to sustain.
Insecticide spraying is not very effective
either, in part because mosquitoes are be-
coming insecticide-resistant. The use of
larvicides—which female mosquitoes them-
selves help spread as tiny clumps of the
powder stick to their body—has not stopped
the epidemic either.
New technologies to control A. aegypti
are on the way. One is the release of mosqui-
toes infected with the Wolbachia bacterium,
which reduces their ability to transmit vi-
GLOBAL HEALTH ruses. The nonprofit World Mosquito Pro-
gram has deployed the mosquitoes in five

Brazil is hoping and waiting for localities in Brazil so far, and the results
are encouraging. Niterói, a city of half a
million where the mosquitoes have been

a new vaccine as dengue rages deployed since 2015, has seen only 58 con-
firmed cases so far this year, compared with
9355 in nearby Rio de Janeiro, with almost
A locally produced vaccine did well in a phase 3 clinical trial 7 million inhabitants. The mosquitoes will
but won’t be available until at least 2025 soon be deployed at more sites, but scaling
up the strategy nationwide is a tall order.
The same is true for the release of sterile
By Marcia Triunfol vaccinate only 3.3 million people this year, male mosquitoes, which mate with females
in a country of more than 220 million. but don’t produce offspring, causing the

W
hen dengue started to circulate
in his small town in the state
of Rio Grande do Sul in Brazil,
Fabio Vilella’s first thought was
that he should get his 13-year-
old son vaccinated. Children are
especially vulnerable, and his son had den-
gue before, which increases the risk of se-
vere disease. But Vilella, an environmental
biologist, soon made a startling discovery:
Not a single private clinic or pharmacy in
the country had any vaccine left. “I’m really
worried,” he says.
Brazil is seeing an unprecedented surge
in dengue, a viral disease that can cause
excruciating pains and is sometimes fatal.
An unusually hot rainy season, along with
rapid, unplanned urbanization, have fueled
its spread this year. Health officials have
reported more than 1 million suspected
cases in January and February, four times
as many as in the same period in 2023, and
A locally produced vaccine could prove to
be better and cheaper, but it will be avail-
able in 2025 at the earliest. “We are fre-
netically working against time,” says Esper
Kallas, director of the Butantan Institute,
which is developing the shot. Brazil has em-
braced new control strategies for the Aedes
aegypti mosquitoes that transmit dengue,
but scaling them up will take time as well.
The dengue virus, which comes in four
different varieties, or serotypes, can cause
high fevers, headaches, painful joints and
muscles, and rash. In some cases it can lead
to severe abdominal pain, bleeding, and
death. This typically occurs when a person
is infected for the second time with a dif-
ferent serotype, in a phenomenon called
antibody-dependent enhancement. Brazil’s
Ministry of Health expects more than 4 mil-
lion dengue cases this year, which would be
a record. Other South American countries
are seeing an uptick in cases as well.
population to crash. One group of Brazil-
ian researchers has created such insects
not with radiation, the usual practice, but
with a cheaper treatment consisting of a
chemical and a bit of double-stranded RNA
that silences a gene involved in male fertil-
ity. An experiment in the city of Ortigueira,
in Paraná state, between 2020 and 2022
resulted in 97% fewer dengue cases when
compared with control cities, the research
team reported last year.
Vaccination is the other promising new
strategy. Takeda’s two-dose vaccine, named
Qdenga and designed to protect against
all four serotypes, contains an attenuated,
or weakened, strain of one serotype as a
“backbone” with genes from the other three
added to it. In trials, the vaccine had an
overall efficacy of 64.2% in people who had
dengue before and 53.5% in those who were
never exposed to the virus.
In February, Brazil’s public health ser-
PHOTO: LUIS NOVA/AP

hundreds have died. But the country has far
too little vaccine to protect its population.
The government cut a deal last year with
the Japanese manufacturer Takeda Pharma-
ceuticals, but it will receive doses to fully
Dengue is notoriously hard to control.
A. aegypti thrives in cities, where water-
filled flower pots, buckets, or discarded
tires make ideal breeding spots. “The mos-
quito loves a water tank in the shade,” says
vice (SUS) started a campaign to vaccinate
10- and 11-year-old children, the group most
at risk of hospitalization from dengue. But
because Brazil is only expecting 6.6 million
Qdenga doses this year, SUS is only target-

1042 8 MARCH 2024 • VOL 383 ISSUE 6687 science.org SCIENCE


ing 521 of Brazil’s municipalities, fewer than
10% of the total. Vaccine uptake has been
modest: Only 32% of eligible children in the
Federal District, and only 18% in Rio de Ja-
neiro, have received their first shot.
The vaccine made in Brazil, named
Butantan-DV, might reach more people.
Originally developed by the U.S. National
Institutes of Health, it contains live strains
of all four dengue serotypes, attenuated by
the removal of a small genome fragment.
It’s a single-dose vaccine, which is “always
preferred,” says Gabriela Paz-Bailey, a den-
gue researcher at the U.S. Centers for Dis-
ease Control and Prevention, because some
people never get their second dose.
In a trial in Brazil among 16,235 people
between ages 2 and 59, published last month
by The New England Journal of Medicine, the
vaccine offered 89.5% and 69.6% protection,
respectively, against two serotypes, DEN-1
and DEN-2, during the first 2 years after im-
munization. There are no efficacy data on
DEN-3 and DEN-4 because no cases were
seen in the study, which is continuing.
But all four weakened serotypes in the
vaccine replicated in more than 50% of vac-
cinated individuals who never had dengue,
notes Andre Siqueira of the Oswaldo Cruz
Foundation. That suggests the Butantan vac-
cine will provide sustained protection for all
serotypes, he says. It is expected to be cheaper
than Qdenga as well. “Once Butantan-DV is
approved and available, the Qdenga vaccine
will be history,” Mello Galliez predicts.
Butantan hopes to apply for approval
to ANVISA, Brazil’s regulatory agency, by
September, Kallas says. Vaccinating the
target population nationwide—those be-
tween 2 and 60 years old—would take some
140 million doses, Kallas says, but he de-
clines to speculate how long that would
take: “I don’t want to create expectations.”
Even after its introduction, the vaccine
will be watched closely. The first approved
dengue vaccine, produced by Sanofi, did
appear to trigger antibody-dependent en-
hancement, like the virus itself, in children
in the Philippines who never had dengue
before and became infected after vaccina-
tion. The country has since banned the vac-
cine. So far, there are no clear signs of the
phenomenon with either the Takeda and
Butantan shots, but it will take more follow-
up to be sure.
“Controlling dengue is very hard,” Paz-
Bailey says. But she believes vaccination,
new mosquito control strategies, and con-
tinued education will eventually help coun-
ter the disease’s surge. “I’m optimistic about
the future,” she says. j
Marcia Triunfol is a science journalist in
Lisbon, Portugal.
SCIENCE science.org
U.S. BUDGET
Final spending bills offer
gloomy outlook for science
Congress makes sizable cuts at key funding agencies
By Science News Staff
S
cientists, prepare to tighten your belts.
This week, the U.S. Congress is ex-
pected to approve six 2024 spending
bills that call for sizable cuts or essen-
tially flat budgets at a number of major
federal research agencies.
The National Science Foundation (NSF)
is the biggest loser, with lawmakers cutting
its budget to $9.06 billion, 8.3% below 2023.
NASA’s science programs will fall by 5.9% to
$7.3 billion. Congress also cut research spend-
ing at the Environmental Protection Agency,
the U.S. Geological Survey, and the National
Institute of Standards and Technology. Sci-
ence programs at the National Oceanic and
Atmospheric Administration and the Depart-
ment of Agriculture remain flat.
The Department of Energy’s (DOE’s) Office
of Science was one bright spot, getting a 1.7%,
$140 million increase to $8.24 billion. But
observers note that boost won’t allow DOE’s
spending to keep pace with inflation.
The bleak numbers are “frankly
unconscionable in an era when we should
be enhancing support for U.S. scientists and
engineers,” says Matt Hourihan, a science
policy specialist at the Federation of Ameri-
can Scientists.
The six bills, which lawmakers had to pass
by 8 March to avoid a partial government
shutdown, mark major progress in resolving
a lengthy impasse over federal spending for
fiscal year 2024, which began on 1 October
2023. Stopgap measures to keep the govern-
ment running largely froze agency budgets at
2023 levels. Reaching a final deal was compli-
cated by a tight spending cap that the White
House and Congress agreed to last year in or-
der to prevent the government from default-
ing on its debt.
The bills meld measures approved earlier
by the House of Representatives and the Sen-
ate. They guide $460 billion in spending,
or about one-quarter of the $1.7 trillion the
nation will spend this year on so-called dis-
cretionary domestic and military programs
(which do not include mandatory programs
such as Social Security). Congress is now rac-
ing to finish the remaining six spending bills
by 22 March. Those bills will set spending for
the National Institutes of Health and the De-
NEWS | I N D E P T H
partment of Defense, two of the nation’s larg-
est funders of research.
At NSF, a budget that is $2.3 billion less
than the $11.3 billion it requested will force
hard choices. Last year, Congress fattened
NSF’s budget with so-called emergency
spending and funds earmarked for the
agency’s new Technology, Innovation and
Partnerships (TIP) directorate, aimed at
commercializing discoveries. Congress envi-
sioned TIP growing rapidly when it created it
in 2022, but this year lawmakers told NSF it
needn’t give it special treatment. As a result,
TIP will compete with the agency’s other re-
search directorates for cash.
At NASA, a 15% cut in the agency’s plane-
tary sciences program, to $2.7 billion, reflects
growing unease in Congress about the rising
costs of several key missions, especially Mars
Sample Return (MSR)—an audacious plan to
ferry soil and rock back to Earth that could
cost up to $11 billion. The Senate proposed
killing MSR, but the final bill instead allows
NASA to spend $300 million to $949 million
on the mission this year. But given the over-
all cut to the planetary science budget, it is
not clear that NASA could reach the higher
amount without cutting other missions.
NASA could soon release a revised MSR plan.
At a NASA advisory meeting this week,
Lori Glaze, the agency’s planetary science
chief, lamented the budget outlook. “This is
going to be a challenge,” she said. “We are al-
ready feeling the effects.”
One item that did not make it into the
final bills was a provision, backed by House
Republicans, that would have blocked the
White House from implementing a 2021
policy to promote public access to scientific
papers and data. Starting in December 2025,
the policy requires federal grantees to deposit
manuscripts of peer-reviewed journal papers
in free, public repositories immediately upon
publication, a change from a policy, favored
by publishers, that has allowed embargoes
of up to 12 months. Lawmakers did call for
an “in-depth” study of the costs of complying
with the new policy; the White House has al-
ready issued two such analyses. j
With reporting by Jeffrey Brainard, Jeffrey Mervis,
David Malakoff, Robert F. Service, Erik Stokstad, and
Paul Voosen.
8 MARCH 2024 • VOL 383 ISSUE 6687 1043
NE WS | I N D E P T H
BIOMEDICINE
Skin side effects stymie advance of HIV vaccine
Strategy of using multiple mRNA shots to hone powerful antibodies hits a pothole
By Jon Cohen
O
ne of the most promising attempts
to reinvigorate the stalled quest for
an HIV vaccine has hit a snag that
might seem minor but has major con-
sequences: delaying the larger trials
needed to show whether the concept
works. In small safety and immune tests of
the innovative vaccine strategy, which re-
lies on a series of messenger RNA (mRNA)
shots, an unusually high percentage of re-
cipients developed rashes, welts, or other
skin irritations.
“We are taking this very seriously,” says
Carl Dieffenbach, head of the Division of
AIDS at the National Institute of Allergy and
Infectious Diseases (NIAID), which funded a
trial of the vaccine. Researchers want to un-
derstand the cause of the skin problems and
how to lessen them before expanding tests of
the vaccines, which are made by Moderna.
“We would be moving more quickly if this
finding had not been observed,” says Mark
Feinberg, who heads IAVI, a nonprofit that is
the vaccine’s major sponsor.
The complex vaccine strategy involves
injections of different mRNAs, encoding
various pieces of HIV’s surface protein or
the entire molecule, over the course of sev-
eral months. The goal is to gradually guide
the immune system’s B cells to produce so-
called broadly neutralizing antibodies, or
bnAbs, capable of stopping many different
variants of the AIDS virus. People living
with HIV on rare occasions eventually pro-
duce bnAbs, but no vaccine has ever done
so—which has become the “holy grail” for
the field, says Linda-Gail Bekker, an AIDS
vaccine researcher in South Africa who runs
the Desmond Tutu HIV Centre at the Uni-
versity of Cape Town.
Different versions of this HIV vaccine have
already gone through three phase 1 trials, but
they totaled fewer than 200 participants. The
recipients responded with B cells making
antibodies with some features of known
bnAbs, fueling hopes for the vaccines. But
skin problems—including urticaria (hives),
pruritus (itching), and dermatographism
(welts after scratching)—occurred at a notice-
ably high level in all of the studies, affecting
11 out 60 people in one of them.
These HIV vaccines deliver a relatively
high dose of mRNA, which Moderna scien-
tists and others think could explain the skin
1044 8 MARCH 2024 • VOL 383 ISSUE 6687
issues. The company’s original COVID-19
mRNA vaccine used the same dose and has
also been linked to skin problems, although
at much lower frequencies, of 1% to 3%. (The
Pfizer-BioNTech collaboration’s COVID-19
vaccine, also based on mRNA but given at
a 70% lower dose, triggers skin problems,
too, but one Swiss study suggests they occur
20 times less frequently than with the Mod-
erna product.) A cumulative effect from mul-
tiple mRNA shots, the genetic background of
the recipients, or the HIV sequences used for
the vaccine could also be responsible for the
welts and hives, and those possibilities are
more worrisome.
Most of these skin problems resolved
quickly and none were severe enough to
stop a trial, but researchers do not want
A vaccine strategy aims to create multiple, powerful
antibodies (various colors) that can attach
to different parts of HIV’s surface protein (gray).
to minimize them. “At a time when vaccine
hesitancy is high, it is critically important
not to dismiss urticaria as an unimportant
side effect,” says Kimberly Blumenthal, an
allergist at Massachusetts General Hos-
pital who has also found a link between
Moderna’s COVID-19 vaccine and higher
rates of urticaria.
Feinberg agrees the side effect issue needs
studying, but is also concerned that people
who are vaccine opponents might mis-
represent the scope of the problem. “This
finding has not been seen to the same fre-
quency with other mRNA vaccines against
other pathogens,” he says.
Had the skin problems in the HIV tri-
als not surfaced, the researchers would
have moved closer to conducting—or even
launched—a study that involved a few hun-
dred people and had a placebo control.
“We’ve hit this rather miserable bump in
the road,” Bekker says.
Multiple research groups are pursuing
similar strategies to create bnAbs. Moderna’s
effort grew out of a project led by biophysicist
William Schief, who developed it at Scripps
Research and then brought the strategy to the
company, where he is now a vice president. It
exploits the fact that B cells begin as naïve, or
germline, cells and then during an infection
undergo a series of mutations that, in effect,
hone the ability of the antibodies they pro-
duce to bind to specific parts of viruses and
“neutralize” their ability to infect cells. The
“germline targeting” vaccine strategy relies
on several shots to take B cells through this
maturation process, eventually leading them
to produce bnAbs against viruses.
“We call it priming, shepherding, and
polishing,” explains Dennis Burton, an
immunologist at Scripps who works with
Schief. Initially the group did not use mRNA.
Its vaccine contained a small piece of HIV’s
viral surface protein attached to a nano-
particle that presented it to the immune
system in a novel way, and early results were
promising. In a 2022 Science paper, Schief
and colleagues reported that 97% of the
36 people who received the vaccine devel-
oped B cell antibody gene mutations that are
first steps toward making bnAbs.
Schief switched to mRNA because it
provides far more flexibility, allowing the
researchers to readily fine-tune the HIV
component of the vaccine. Because of the
enormous diversity of HIVs in circulation,
he contends that an effective vaccine likely
will have to trigger production of up to five
different bnAbs. That would mean prim-
ing, shepherding, and polishing multiple B
cell lineages. Without the easy-to-modify
mRNA, Schief says, “good luck—that is a
daunting, daunting task.”
NIAID now plans to repeat the phase 1
PHOTO: LARS HANGARTNER AND CHRISTINA CORBACI
trials of these Moderna HIV vaccines with
a lower dose. Bekker, who lives in a country
that has more people living with HIV than
any other, is still hopeful the approach will
pan out. “We’ve got to chapter one of an
exciting novel.” After decades of failed at-
tempts to develop an HIV vaccine, the goal
remains pressing, she says. “Last year, the
world had 1.3 million infections of HIV. I
think it remains an urgent requirement to
find a good solution.” j
science.org SCIENCE
 2023 Winner
Marissa Scavuzzo, Ph.D.
Case Western Reserve
University School of
Medicine, Cleveland, USA
For research on glial
cells in the gut
Call for Entries 2024
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The annual Eppendorf & Science Prize for
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FEATURES

PHOTO: CREDIT GOES HERE AS SHOWN; CREDIT GOES HERE AS SHOWN

THE RECKONING
Didier Raoult and his institute found fame during the pandemic.
Then, a group of dogged critics exposed major ethical failings
 By Cathleen O’Grady
W
ith six studies published
in the 2010s, French micro-
biologist Didier Raoult added
to his already vast publication
record. He and his colleagues
conducted a wide range of
investigations into infectious
diseases and their treatments.
They took stool samples from
patients on long-term antibiotic treatment,
looking for alterations in their gut micro-
biome. They swabbed the throats of pilgrims
leaving France for Mecca, searching for evi-
dence of a bacterium that causes brain ab-
scesses. And they studied samples of heart
valves and blood clots from patients with
heart inflammation to refine tests for the
bacteria that cause the condition.
But in January, the American Society for
Microbiology (ASM) journals that published
the papers announced they were retracting
all six, along with a seventh by Raoult’s col-
leagues. Aix-Marseille University had inves-
tigated the research, which was done at its
affiliated Hospital Institute of Marseille Med-
iterranean Infection (IHU), a research hos-
pital that Raoult led until his retirement in
2021. The investigation found the work had
not been reviewed by one of France’s highly
regulated national ethical committees. It was
therefore in violation of French law and the
Declaration of Helsinki, an international eth-
ics document that guides clinical research.
In a written statement sent to Science,
Raoult says ASM retracted the papers with-
out accounting for his team’s rebuttals to
the critiques. But to Lonni Besançon, the re-
tractions are vindication of concerns that he
and others have been voicing since Raoult
and the IHU burst into the media spotlight
in the early days of the COVID-19 pandemic,
downplaying its severity and touting pros-
pects for a successful treatment.
The Linköping University computer sci-
entist and his fellow critics—a gaggle of
dogged individuals, many of them academic
outsiders—originally set out to challenge
PHOTO: CREDIT GOES HERE AS SHOWN; CREDIT GOES HERE AS SHOWN
poor-quality research coming out of the IHU,
especially the claim that COVID-19 could be
treated with the antimalaria drug hydroxy-
chloroquine (HCQ). But they soon embarked
on an all-consuming attempt to raise the
alarm about ethical failings in the institute’s
ILLUSTRATION: SARA GIRONI CARNEVALE
research, going back at least 15 years.
Their efforts have met with lackluster re-
sponses from France’s scientific institutions,
Besançon says, but the retractions are the
most important consequence so far. They
“confirm what we suspected,” he says. “But I
am hoping that things will go further.”
Raoult says his critics are stalkers and
cyberharassers who have misunderstood
how French biomedical law works. He says
he’s followed ethical regulations and that
much of the research under fire has been on
“human waste”—such as fecal matter—which
is not defined as biomedical research under
French law.
But the ethical failings are “not dis-
puted” within the scientific community, says
Philippe Amiel, a lawyer who specializes in
human experimentation. The authorities
have known about problems at the IHU for
years, adds Karine Lacombe, an infectious
disease specialist at Sorbonne University. If
they had acted earlier, she says, “the picture
of the pandemic in France would have been
totally different.”
A criminal investigation of Raoult’s insti-
tute is now underway. But his critics are ask-
ing why French institutions took so long to
tackle systemic violations at the IHU, leaving
it to a persistent group of outsiders to inves-
tigate the institute and push for punitive ac-
tion. And they are wondering whether Raoult
and the institute will be held to account for
the wide range of lapses they have alleged.
“It’s a big, big mess,” Lacombe says.
RAOULT IS BEST KNOWN for his work on
rickettsia—bacteria transmitted by fleas
and ticks—and his discovery of giant vi-
ruses. He has accumulated national decora-
tions in both France and his birth country
of Senegal as well as prestigious scientific
awards, including the 2010 Grand Prize
from the French biomedical research
agency INSERM. He has published prolifi-
cally, with more than 3200 papers indexed
on PubMed, and is one of the most highly
cited researchers in his field.
In 2011, Raoult was selected to lead
the newly created IHU in Marseille, one
of six state-of-the-art research hospitals
established by then-President Nicolas
Sarkozy’s government. Raoult’s IHU, which
specializes in infectious disease research,
was launched with a €72 million govern-
ment grant, and in 2018 it moved into an
imposing new building. The institute’s
power is political as well as scientific, says
Michel Dubois, a sociologist of science at
the French national research agency CNRS:
“When you open this institute—when you
create a building—you need some leverage
at the political level.”
As Europe began to pay serious attention
to the COVID-19 pandemic in early 2020,
the media wanted to know what Raoult
and his institute made of the situation. “Al-
most every day, you were able to watch a
new interview with Raoult,” says Antoine
Bristielle, a social scientist at the Jean-
Jaurès Foundation, a think tank. “It became
8 MARCH 2024 • VOL 383 ISSUE 6687 1047
NE WS | F E AT U R E S
a self-reinforcing phenomenon … the me-
dia were interested in what he was saying, so
he came to be really powerful in the French
population. And then, of course, the media
wanted him because he was able to attract
large audiences.”
In videos posted online by the IHU,
Raoult is often seated in an office, wearing
a lab coat, long gray hair and beard slightly
unkempt. He speaks soberly and quietly,
frowning slightly while delivering reassuring
pronouncements: The new coronavirus has
a mortality rate not too different from wide-
spread respiratory infections; a treatment
will be coming soon.
Raoult’s confident statements caught the
eye of Fabrice Frank, a former biologist who
had left academia and become a high school
math and physics teacher. By the time the
pandemic hit, Frank had moved from France
to Morocco, where he started an IT company
and dedicated his spare time to surfing. He
watched with shock when Raoult asserted—
with minimal evidence, based on thinly re-
ported research in China—that HCQ, or the
related medicine chloroquine phosphate,
would be an effective treatment.
Victor Garcia, a journalist at French
magazine L’Express, saw scientists express-
ing skepticism about Raoult’s claims on
social media. He called the IHU, assum-
ing it had more details that could counter
some of the critics’ concerns. But Garcia
says he received a “strange” response from
IHU researcher Jean-Marc Rolain. “I am a
scientist,” Rolain said. “If I tell you to take
chloroquine, you’ll listen to me.” (Rolain did
not respond to multiple requests for com-
ment.) That was “the beginning of me ask-
ing questions,” Garcia says.
ON 11 MARCH 2020, French health minister
Olivier Véran invited Raoult to join the Scien-
tific Council advising the government on its
A slow-motion downfall
Critics first raised concerns about ethical approvals for Didier Raoult’s studies in early 2020, as the COVID-19 pandemic catapulted the Hospital Institute
of Marseille Mediterranean Infection (IHU) to prominence. They say French authorities and journals have taken far too long to react.
20 March 24 March
The IHU publishes a paper Scientific integrity
reporting that hydroxychlo- sleuth Elisabeth Bik
roquine (HCQ) is effective at notes issues
treating COVID-19. with HCQ paper.
25 March
Mathieu Molimard and French
Society of Pharmacology begin
posting online about HCQ
ineffectiveness and risks.
1048 8 MARCH 2024 • VOL 383 ISSUE 6687
Elisabeth Bik, a scientific integrity sleuth based in
San Francisco, first raised concerns about the Hospital
Institute of Marseille Mediterranean Infection’s (IHU’s)
work on hydroxychloroquine (HCQ) in March 2020. She
went on to identify major ethical and scientific issues
in dozens of IHU papers, spurred on, she says, by abuse
from Didier Raoult and his supporters.
pandemic response. A few days later, Raoult
and his team published a bombshell paper in
the International Journal of Antimicrobial
Agents, reporting that the IHU had found
HCQ combined with the antibiotic azithro-
mycin to be an effective COVID-19 treatment.
Although the results were preliminary and
other researchers doubted Raoult’s conclu-
sions, HCQ hype surged, with then–U.S. Pres-
ident Donald Trump touting its promise and
Raoult enthusing over it on YouTube. “Raoult
was saying, ‘I understand everything, I have
a solution,’ and people want that kind of in-
formation in troubled times,” Bristielle says.
Raoult’s popular support bred political
support, Bristielle adds. “If someone has
such a presence in the media landscape,
politicians have to listen to him—otherwise
they will be really distrusted by the popula-
tion.” On 26 March—amid strong resistance
from some other members of the scientific
council—Véran issued a decree allowing HCQ
27 March 8 April
Second IHU Drug safety agency
study on HCQ quizzes the IHU about
published ethical approval in
as a preprint second HCQ study.
2020
26 March Early April
French health minister Tipster alerts French
Olivier Véran allows drug safety agency to
HCQ to be prescribed ethical concerns in
to COVID-19 inpatients. HCQ research.
to be prescribed to COVID-19 inpatients.
Scientific integrity consultant Elisabeth
Bik decided to take a close look at the HCQ
paper. A microbiologist by training, Bik al-
ready knew of Raoult and his reputation for
prolific publication. On her blog she pointed
to several problems she saw with the paper:
Patients had not been randomly assigned
to the treatment and control groups, which
could have biased the results. She also noted
that six patients out of the 26 treated with
HCQ were dropped from the data—including
three who were transferred to intensive care
and one who died—which painted a more fa-
vorable picture of the treatment.
Besançon, too, was curious. He looked into
the paper, which had been submitted to the
journal on 16 March and accepted the next
day, and noticed that one of the authors was
also editor-in-chief at the journal. “So you
have a very short reviewing time and edito-
rial conflict of interest,” he says. “I just find
this potentially a big red flag. But I thought,
it’s just one paper.” (A July 2020 editorial in
the journal said handling of the paper had
been delegated to an associate editor to mini-
CREDITS: (TIMELINE) M. HERSHER/SCIENCE; (ILLUSTRATIONS) N. BURGESS/SCIENCE
mize potential bias, although it noted that
“some of the concerns regarding the paper’s
methodology were substantiated.”)
Over the next few weeks, two more IHU
studies appeared, with unusually short peer-
review timelines, both in a journal where
one of the authors was an associate editor.
One of those papers was a second study
using HCQ to treat 80 “mildly infected”
hospitalized COVID-19 patients; nearly all
improved clinically. The study had not been
reviewed by one of France’s 39 Committees
for the Protection of Persons (CPPs), the
highly regulated independent ethics com-
mittees authorized to approve biomedical
research. Instead, it had been approved by
the IHU’s internal ethics committee.
This was sufficient, the authors wrote,
26 May 12 November
France withdraws Marseilles public prosecutor
approval of HCQ closes case on HCQ papers,
as a COVID-19 saying there has been no
treatment. legal breach.
2021
30 October
Pharmaceutical company
Sanofi reports that
the IHU continues to
place large HCQ orders.
science.org SCIENCE
Another random document with
no related content on Scribd:
 »Jane ei ole enää mikään lapsi; sitäpaitsi ei teillä ole
aavistustakaan, miten vähän arvoa liinalla on tämmöisessä
tapauksessa. Kas niin, nyt teidän täytyy laskea kuningatar liikkeelle.»

Ballmann seisoi Hannan vieressä.

»Mikä ihana ilta!» sanoi hän liikutuksesta väräjävällä äänellä.

Hanna myönsi. Nyt seurasi hiljaisuuden tuottama lumous, joka on

sitä vaarallisempi, kuta kauemmin se kestää, — joka on
salaperäisempi kuin kuiskaus, intohimoisempi kuin huuto.

»Minulla ei ole mitään syytä liikuttaa kuningatarta», sanoi tohtori.

»Siirränpä tästä tämän talonpojan. Mutta teidän salaperäisiä
sanojanne siitä, että liina tässä erikoisessa tapauksessa on
tarpeeton, en ymmärrä. Jos kaksi nuorta ihmistä, jotka niin selvästi
rakastavat toisiaan, jätetään samppanjapäivällisten jälkeen
kahdenkesken penkereelle ja vielä kuutamoisena kesäkuun-
iltana…»

»Niin se on vaarallista…»

»Sitä aioin juuri sanoa.»

»Minusta teidän talonpoikanne tuossa on vaarallinen, sillä se

ahdistaa hevostani. Mutta te puhutte siksi paljon tyhmyyksiä, ettei voi
tehdä edes kunnollista siirtoa. Mitenkä sitten voisi pelata
järjestelmällisesti? No niin, minä muutan tornin ja uhraan hevosen.»

Oliko Ballmann vetänyt Hannan luokseen vai oliko tämä

heittäytynyt hänen syliinsä? He eivät sitä tienneet. Hannan pää
lepäsi Ewaldin olkaa vasten, ja tämä oli kiertänyt kätensä hänen
ympärilleen. Orkesteri soitti Gretchenin ihanaa antaumislaulua.
 Shakkipeli oli sillä välin jatkunut. Pelaajat olivat syventyneinä
laskelmiinsa; he eivät puhelleet enää, vaan miettivät, miten voisi
uhkaavaa tappiota välttää. Shakkipöydän ääressä vallitsi
mielenkiinnon hiljaisuus… penkereellä onnen syvä rauha.
XXXV.

Seuraavana päivänä Hanna sai kirjeen. Hän arvasi heti, että se oli
Ballmannilta, ja aukaisi nopeasti kuoren. Paperi vapisi hänen
kädessään, kun hän luki:

»Rakkain! — tai — niinkuin minä oikeastaan vain saisin sanoa:

Arvoisa neiti! Tunnen syyllisyyteni, tunnen rikollisuuteni edessänne.
Minun olisi jo heti ensimäisenä päivänä pitänyt sanoa teille jotain,
mutta en ole voinut saada sitä huulieni yli, ja nyt nämä rivit kertovat
sen teille: Minä olen naimisissa. Minulla ei ollut oikeutta koettaa
voittaa sydäntänne, mutta kaipaako rakkaus muuta kuin
vastarakkautta? En kuitenkaan tahdo puolustaa itseäni.
Aikomukseni on vain teille ilmaista kauan salaamani totuus,
nimittäin että olen naimisissa. Ja kuitenkaan ei minulla ole vaimoa
eikä kotia. Noin kymmenen vuotta sitten hän jätti minut
seuratakseen rakastajaansa. Siitä saakka en ole kuullut hänestä
mitään. En edes tiedä, elääkö hän. Hänen kuvansa on säilynyt
mielessäni kuin utukuva… Hän oli kaunis, niin kaunis että hän
jonkun verran muistutti teitä, Jane. Tämä yhdennäköisyys ensin
hämmästyttikin minua, kun teidät näin. Ja kuitenkin, miten
toisenlainen hän oli! En tarkoita niin paljon hänen ulkomuotoansa;
ero on teidän sielukkaassa katseessanne, teidän vakavassa
ilmeessänne, teidän jalon mielenne heijastuksessa, jota kaikkea
minun lapselliselta, kevytmieliseltä vaimoltani puuttui. Katuvaisena
odotan tuomiotanne rikoksellisesta vaitiolostani. En voi uskoa, että
meidän täytyisi ainiaaksi erota… Täytyy olla keinoja, jotka tekevät
meidän yhteenliittymisemme mahdolliseksi. Kuulutanko uskottoman
jälkeen? Ehkei hän enää eläkään… ehkä avioero on mahdollinen…
tai ehkä rakkautemme on kyllin vahva repimään alas esteet? Miten
tulee käymään, Jane? Päättäkää! Elämäni, olemassaoloni lasken
— sinun käteesi!

Ewald Ballmann.»

Miten olisi kirjeenkirjoittaja hämmästynytkään, jos hän olisi nähnyt

hymyn, joka nousi Hannan huulille hänen lukiessaan kirjettä, joka
kirjoittajan mielestä oli antava hänelle kauhean iskun!

»Nyt kai olen pakotettu antamaan itseni ilmi, täti?» sanoi Hanna
luettuaan kirjeen ystävälleen. »Minusta on vain hiukan harmillista
alentua mustatukkaisesta, 'sielukkaasta' Janesta vaaleakiharaiseksi,
kevytmieliseksi Hannaksi…»

»Sitä en tekisi vielä, jos olisin sinun asemassasi. Niin äkkiä

tapahtunut naamarin riisuminen saisi hänet pettymään. Minä sitoisin
hänet vielä lujemmin… minä koettaisin saada hänet, niin rakastunut
kun hän on, ehdottamaan sinulle jotain, joka muistuttaisi sinun
pakoasi, sillä silloin… Mutta en oikein itsekään tiedä, mitä sinulle
neuvoisin… tämä on niin eriskummallista…»

Palvelija ilmoitti tohtori Scherenbergin. Hanna nousi.

»Menen huoneeseeni vastaamaan tähän», hän sanoi.

 »Miten iloiselta näytätkään, Jane…»

»Niin, en koskaan olisi luullut elämän olevan niin ihanaa. Mutta nyt
minä menen ja jätän tohtorin teille.»

»No, rakas Scherr, mitä teidän juhlallinen, tyytymätön ilmeenne

ennustaa? Onko ihmiskunta saanut tietää, miten tyhmänä te sitä
pidätte, ja siitä suuttunut?»

»Ikävä ja mieltäjärkyttävä on koko juttu, mutta sillä on vakava

puolensa, joten katson olevani velvollinen teille siitä ilmoittamaan»,
sanoi tohtori puristettuaan Mrs. Edgecomben kättä ja istuuduttuaan
häntä vastapäätä.

»Minä olen vallan utelias. Puhukaa!»

»No niin, sanon sen suoraan kiertelemättä. Te tulette hyvin

hämmästymään. Amerikkalaisemme on tänään tunnustanut minulle,
että hänellä on vaimo.»

»Ah!»

»Mitä te sanoitte?»

»Sanoin 'ah'…»

»Ettekö mitään muuta?»

»Mitäpä minä muuta sanoisin?»

»Ainakin 'tuhat tulimmaista'!»

»Jos se huvittaa teitä, niin voinhan sanoa vielä jonkun muunkin

voimasanan.»
 »Te nauratte, Mrs. Edgecombe, mutta luulisin asian olevan
vakavaa laatua. Eilisen kuherruksen ja sen edellisen pitkän
armastelun olisi luullut saavan vallan toisen käänteen. Jospa teidän
veljentyttärenne sydän ei olisi kuoliaaksi haavoitettu eikä hänen
maineensa kärsisi siitä! Tämä mies ei tietenkään koskaan enää saa
astua jalallaan tähän taloon… Voitteko antaa minulle anteeksi, että
olen tuonut hänet tänne?»

»Älkää innostuko liiaksi, Scherr! — Luulin teillä olevan vapaampia

ja harkitumpia mielipiteitä sydämen asioissa.»

»Mielipiteet kyllä, hyvä Mrs. Edgecombe; jos on kysymys

ihmiskunnasta yleensä, olen valmis ivailemaan sen häveliäisyyttä,
mutta käytännössä täytyy mukautua vallitseviin tapoihin ja tehdä
voitavansa suojellakseen hyviä ystäviään.»

»Tahdotteko, niin hämmästytän teitä vielä enemmän, rakas tohtori,

kertomalla teille jotain, joka saa teidät huudahtamaan ei ainoastaan
'tuhat tulimmaista', vaan paljon kovempaakin?»

»Entä mitä se sitten on?»

»Että Janella on mies.»

Tohtori hätkähti. »Neiti Jane — naimisissa!»

»Ei siinä vielä kylliksi, rakas ystävä. Teidän hämmästyksenne on

oleva rajaton, kun kerron kuka on veljentyttäreni — hän ei muuten
olekaan veljentyttäreni — kun sanon kuka on Janen mies.»

»Kuka se sitten on? En voi enää hämmästyä enempää. Jos Jane

neiti on naimisissa, olkoon hänen miehensä vaikka suur'moguli tai
paavi itse…»
 »Silloin ei asia olisikaan niin lystikäs kuin todellisuudessa. Janen
mies on Ewald Ballmann — siis teidän amerikkalaisenne.»

Mrs. Edgecombe kertoi nyt vanhalle ystävälleen koko asian. Hän

tiesi voivansa luottaa hänen vaitioloonsa.

»Asia on nyt Hannan käsissä», sanoi hän lopuksi, »eikä meidän

pidä siihen sotkeutua. Teidän täytyy antaa kunniasananne, ettette
kerro mitään Ballmannille.»

Hanna oli sillä välin väärennetyllä käsialalla kirjoittanut kirjeen

miehelleen. Hän pyysi häntä heti saapumaan luokseen, koska tahtoi
puhua hänen kanssaan kahdenkesken. Hänen tuli mennä
huvihuoneeseen puutarhaveräjän kautta.

Tässä puutarhan kaukaisimmassa sopessa olevassa

huvihuoneessa Hanna häntä odotti. Huvihuoneen avoimia ikkunoita
ympäröi kukkiva kuusamapensaikko; oksien varjot tanssivat
niinimatoilla peitetyllä lattialla. Hanna istui sohvalla, joka ympäröi
seiniä, ja katseli kaipaavasti ovea kohden. Tuskin oli kymmenen
minuuttia kulunut, ennenkuin hän kuuli Ewaldin askeleet. Rajusti
sykkivin sydämin hän nousi, ja samassa oli odotettu kynnyksellä.
Taas hänen täytyi hillitä itseään, ettei heittäytyisi hänen syliinsä. Hän
nojasi toisella kädellään viereiseen pöytään ja viittasi estävästi
toisella, kun Ewald riensi hänen luokseen huudahtaen: »Jane —
Jane!»

»Te työnnätte minut luotanne? Siksikö pyysitte minua tulemaan

tänne?»

»Mielestäni meidän välillämme ei voi tulla kysymykseen muu kuin

ero…
Te ette ole vapaa…»

Hanna astui muutaman askeleen taaksepäin ja istuutui sohvalle.

»Ero?» toisti Ewald. »Voiko ajatella eroa, kun tuskin vielä lausutut
sanat 'minä rakastan sinua' ovat huulillani? Tai vihaatteko minua,
halveksitteko minua? Onko tieto rikollisesta vaitiolostani voinut
sammuttaa eilisen rakkaudenhehkun?»

»Minulla ei ole minkäänlaista oikeutta halveksia teitä, sillä

minäkään en ole ollut avomielinen teitä kohtaan ja sitä sanoakseni
olen kutsunut teidät tänne. En ole nuori neitonen, kuten luulette…
minäkin olen naimisissa…»

Ewald hätkähti.

»Naimisissa!» huudahti hän.

»Niin. Ja mikä vielä pahempi, minua ei ole hyljätty, vaan olen itse
hyljännyt. Siitä on noin kymmenen vuotta sitten kun viimeksi näin
mieheni…»

»Te olitte siis onneton?»

»Olin. Me emme sopineet toisillemme. Mieheni oli… niin, mitenkä

sanoisin?… kuiva, kylmä… niinkuin te olitte ollut, kuten ensi
käynnillänne kerroitte… ujo, runoutta pelkäävä.»

»Niin, minä ymmärrän… semmoinen kuin minä kerran olen ollut.

Mitenkä huonosti semmoinen mies onkaan sopinut teille! Ja te
pakenitte ilottomasta kodista? Yksinkö?»

Hanna oli vaiti.

 »Yksinkö?» toisti Ballmann, »tai onnellisemman kanssa, joka teille
paremmin sopi? Jane, vastaa!»

»Minä en tahdo vastata siihen kysymykseen. Kauan aikaa sitten

tapahtuneesta en ole velvollinen tekemään tiliä sille miehelle, jota
eilisestä saakka rakastan.»

»Rakastat ja vielä rakastat, eikö totta?» huudahti Ballmann

intohimoisesti sulkien nuoren naisen syliinsä. »Eikö totta… te
rakastatte minua vielä ja ainiaan?»

Hanna ei vastustellut, vaan nyökäytti päätään hymyillen.

»Sinä olet oikeassa», jatkoi Ewald. »Menneisyys on kuin usva,

joka on haipunut pois; nykyisyys on meidän. Semmoisena kuin nyt
olet, rakastan sinua.»

Hanna irroitti itsensä hänen syleilystään.

»Niin, tällä hetkellä», hän sanoi, »mutta ajattele tulevaisuutta! Mikä

on oleva kohtalomme?»

»Katsokaamme rohkeina tulevaisuutta silmiin!» vastasi Ballmann.

»Paetkaamme!»

Hanna hymyili. Hän muisti ystävättärensä sanat. Nyt ne olivat

täyttyneet.

»Paetkaamme!» toisti Ballmann innokkaasti. »Lähtekäämme

uuteen kotimaahani, Amerikkaan, ja jättäkäämme nämä ahtaat olot
täällä. Siellä ei kukaan tunne suhdettamme, ja me elämme vain
toisiamme varten. Minä olen kyllin rikas suojataksemme meitä
puutteelta… Solmikaamme vapaan rakkauden liitto! Tahdotko,
Jane?»

Mutta hän ei saanut kauempaa odottaa vastausta. He kuulivat

lähestyviä askeleita ja ääniä. Mrs. Edgecombe, joka ei tiennyt
Hannan ja Ballmannin kohtauksesta, oli lähtenyt tohtorin kanssa
kävelemään puutarhaan ja aikoi levähtää huvimajassa.

»Vai niin, oletko sinä täällä, Jane? Ah, hyvää huomenta, herra
Ballmann!»

Tohtori astui sisään Mrs. Edgecomben jälkeen ja ojensi kätensä

Hannalle. Hänen poskensa, jotka jo muutenkin olivat punaiset,
punastuivat vielä enemmän hänen ajatellessaan, mitä tohtori voisi
ajatella heidän täällä-olostaan kahdenkesken, mutta sitten hän
naurahti, sillä hänen kaksinpuhelunsa oli niin oikeutettua. Mrs.
Edgecombe ja tohtori Scherenberg eivät voineet olla vaihtamatta
keskinäisen ymmärtämyksen katsetta. Ainoa hämillään oleva oli
Ballmann; hänestä tuntui, kuin hänet olisi saatu verekseltä kiinni.

He vaihtoivat muutamia jokapäiväisiä sanoja; sitten Mrs.

Edgecombe ehdotti, että he palaisivat takaisin huvilaan. Hän meni
edellä tohtorin taluttamana; Hanna ja Ballmann tulivat jonkun matkan
päässä.

»Myönnytkö vai kieltäydytkö?» hän kuiskasi.

»Mene nyt. Tahdon olla yksin ajatuksineni. Annan vastaukseni

sittemmin.»

»Jane, sinä et pääse minusta; sinä olet minun; tunnen sen.»

»Minäkin luulen sitä melkein… mutta mene nyt.»

 Ewald totteli. Kun he saapuivat huvilalle, ei hän Mrs. Edgecomben
kutsusta huolimatta jäänyt, vaan kiiruhti pois.

»Minä tulen kanssanne, Ballmann», sanoi tohtori ja suuteli Mrs.

Edgecombea kädelle.

Molemmat herrat poistuivat, ja Mrs. Edgecombe ja Hanna menivät

sisään.

»Kello neljän junassa. Kun Ewald on saanut vastaukseni, lähtee

hän aikaisemmassa junassa ja odottaa minua määrätyssä
paikassa.»

»Niin, näen hänen valmistaneen kaiken», sanoi Mrs. Edgecombe

luettuaan Ballmannin kirjeen. »'Frankfurt, Hotel Westendhall! Jos
joku nainen kysyy ovenvartialta huonetta rouva Ewaldille, on tämä
vievä hänet, maailman onnellisimman miehen luo' j.n.e…» sanoi
Mrs. Edgecombe jättäen kirjeen takaisin. »Hotel Westendhallissa te
siis olette päättäneet tavata? Muistatko, että asuimme samassa
hotellissa, kun kaiken maailman asiamiesten kautta koetimme saada
selkoa samaisesta herra Ewaldista? Kuka olisi voinut aavistaakaan,
että hän kerran 'maailman onnellisimpana' odottaisi sinua siellä?
Useimmiten käy kaikki aivan toisin kuin on ajateltu tässä
maailmassa.»

Kello puoli neljältä vaunut olivat oven edessä ja palvelija nosti

Hannan matkalaukun niihin.

»Jo valmiina matkapuvussa, rakas lapsi?» huudahti Mrs.

Edgecombe, kun Hanna astui hänen huoneeseensa. »Näyttää siltä,
kuin pakosi onnistuisi erinomaisesti.»
 »Tulen sanomaan hyvästi…»

»Hyvästi sitten, Jane!… Minun Janeni menee ja takaisin palaa

ainoastaan hänen Hannansa.»

Hanna oli hyvin liikutettu. Tässä silmänräpäyksessä hän unohti

Ballmannin tapaamisen, joka jo etukäteen oli tuottanut hänelle niin
sanomatonta iloa, ja ajatteli vain eroa ystävästään.

»Hyvästi, ainoa, paras ystäväni!… Nyt kun pian saan onneni

ainiaaksi, täytyy minun kiittää sinua, täti, kaikesta mitä olet ollut
minulle… suojani, tukeni, hädästä pelastajani… Sinua minun tulee
kiittää kaikesta, kaikesta.»

Hanna oli puhuessaan heittäytynyt polvilleen Mrs. Edgecomben

viereen ja suuteli itkien hänen kättään.

»Jane, Jane… rakas lapsi! Minunkin täytyy kiittää sinua siitä ilosta,
minkä olet minulle suonut. Nouse ylös, rakkaani! Älä myöhästy
junasta. Kas, tässä on kirje, joka sinun tulee ottaa mukaasi. Lupaa
minulle, ettet avaa sitä, ennenkuin miehesi on jälleen puolisosi.
Lukekaa se yhdessä.»

Hanna otti kirjeen ja antoi pyydetyn lupauksen. Hän pyyhki

kyyneleensä, suuteli useamman kerran ystäväänsä ja kiiruhti
vaunuihin.

»Rautatieasemalle!» sanoi hän. Sitten hän vielä kerran katsahti

Mrs. Edgecomben ikkunaan. Tämä oli tullut parvekkeelle ja huiskutti
nenäliinaansa.
XXXVI.

»Onko huone rouva Ewaldille kunnossa?» kysyi Hanna ovenvartialta

Hotel
Westendhallissa.

»On, Herra Ewald on jo tullut. Hän on tilannut huoneen ja odottaa

rouvaa… Vahtimestari, viekää rouva N:o 12:een!»

Rajusti sykkivin sydämin Hanna meni palvelijan perässä rappusia

ylös.
Tämä avasi oven, antoi Hannan astua sisään ja sulki sitten jälleen
oven.

Hanna kuuli ilohuudon, ja kahdet käsivarret ojentuivat häntä

kohden. Mitä kahdella rakastavalla on toisilleen ensiksi sanottavaa,
sitä eivät voi muut kuin suudelmat kertoa. Ei ole sanoja, jotka niin
selvästi kertoisivat heidän tunteistaan.

Hetkisen kuluttua Hanna irtaantui tästä syleilystä. Hän riisui

hansikkaat ja hattunsa ja katsahti ympärilleen huoneessa. Se oli
hienosti sisustettu sali. Uuninreunalla olevat maljakot olivat täynnä
kukkia, ja sohvan edessä olevalla pöydällä oli myöskin kukkia, ja
sitäpaitsi oli siihen katettu kahdelle.
 »En voi käsittää onneani», sanoi Ewald. »Entä sinä? Sano,
tunnetko itsesi oikein onnelliseksi?»

»En oikein. Puuttuu vielä jotain. Minun täytyy puhua kanssasi

eräästä hyvin tärkeästä asiasta, ja tästä keskustelusta riippuu,
tulenko minä… tuletko sinä olemaan täysin onnellinen.»

Hanna oli istuutunut uunin vieressä olevaan nojatuoliin, ja

Ballmann seisoi nojaten uuninreunaan ihastuneena katsoen häneen.

»Täysin onnellinen?» toisti hän. »Pelkään sinun ajattelevan jotain,

joka ei ole mahdollista maan päällä. Voin kyllä aavistaa, mikä sinua
tekee levottomaksi, mikä vie nousevan lemmenaurinkomme
pilveen… Minähän voin lukea ajatuksesi kuin avoimesta kirjasta.
Jotta niin hyvä, niin rikkailla luonnonlahjoilla varustettu nainen kuin
sinä voisi tuntea täydellistä sisäistä tyydytystä, täytyy hänen tuntea,
ettei siveyttänsä loukata. Ja tämän uhrin sinä minulle kannat. Sinä
luovut omaisiesi kunnioituksesta ja annat kohtalosi minun käteeni;
sinä saatat vanhan ystäväsi murheelliseksi; sinä tiedät, että
kyyneleitä vuodatetaan sinun tähtesi, että olet syypää vihaan ja
tuskaan, ja näistä johtuvat ajatukset heittävät varjon sille tielle, jolle
olet astunut, miten sitä valaiseekin rakkautemme. Olenko oikeassa,
Jane? Olenko ymmärtänyt sinua?»

»Minä tuntisin kai niin, jos asiat olisivat sillä tavoin kuin luulet.
Mutta sinä et voi tietää mikä minua huolestuttaa, ennenkuin olen
puhunut suuni puhtaaksi. Anna minun ensin kuitenkin tehdä sinulle
joitakuita kysymyksiä ja lupaa minulle, että vastaat niihin
totuudenmukaisesti.»

»Sen lupaan mielelläni. Mitä tahdot tietää?»

 »Ensiksikin tahtoisin tietää, eikö loukattu velvollisuudentunto
vaivaa sinuakin tänä hetkenä. Mitä sinä olet tehnyt, ei sekään ole
aivan oikein…»

»Olen luvannut olla sinulle täysin avomielinen. Tiedän hyvin, etten

ole tehnyt oikein, mutta ettäkö se vaivaisi minua tänä hetkenä? Ei.
En olisi mies, jolle ihanin nainen tahtoo kuulua, jos tällä hetkellä
tuntisin omantunnon tuskia… Tiedän varsin hyvin menetteleväni
väärin, mutta teen sen mielelläni. Ajattelehan janoavaa, joka pitkän
erämaamatkan jälkeen löytää raikkaan lähteen. Luuletko hänen
voivan olla juomatta siitä, joskin siitä seuraisi kuolema? Ei, Jane,
taivaan autuuden menettämisen uhallakaan en tahtoisi olla vailla
tämän hetken onnea.»

Hän tahtoi kumartua vahvistaakseen sanojaan suudelmalla, mutta

samassa koputettiin oveen ja palvelija astui sisään alkaen valmistella
päivällistä. Hän veti eteen ikkunaverhot, sytytti kynttilät ja asetti ne
pöydälle.

»Saanko tarjota päivällisen?» hän kysyi.

»Ei vielä, me soitamme.»

Kun palvelija oli poistunut ja Ewald uudelleen tahtoi kumartua

Hannan puoleen, nosti tämä kätensä estäen eteen ja sanoi:

»Ei, ei. En tahdo suudelmaa, joka ei tarkoittaisi minua yksin.»

»Minä en ymmärrä…»

»Istuudu tähän, Ewald, minua vastapäätä ja anna minun koota

ajatuksiani…»
 Hän pudisti hymyillen päätään ja istuutui.

»Kuule nyt tarkkaan, mitä minulla on sinulle sanottavana. Minulla

on niin paljon, paljon puhumista. Mutta anna minun vielä tehdä
sinulle yksi kysymys. Etkö koskaan ajattele vaimoasi? Tai jos niin
teet, mitä silloin tunnet?»

»Sinä kai pelkäät, että muisto hänestä voisi häiritsevästi vaikuttaa

suhteeseeni sinuun?»

»Älä kysele kysymykseni alkujuurta, vaan vastaa.»

»No hyvä. Sanon sinulle koko totuuden. Vaimoni ajatteleminen on

ainoa soraääni onnessani. Siihen sekoittuu kai katumusta…»

»Katumusta… miten niin?»

»Minusta tuntuu, kuin olisin syyllinen… hänen suhteensa. Enkö

menetellyt julmasti, kun noin vain ilman muuta ajattelin häntä
kuolleeksi, kun en alkanut tiedustella, minne hän oli joutunut, kun en
jättänyt kotiani hänelle auki, jos katumus tai hätä olisivat tuoneet
hänet jälleen luokseni? Kukapa tietää… Ehkä hän sortui, kun ei
löytänyt paluun mahdollisuutta… ehkä hän on kuollut rukoillen
anteeksiantoa, enkä minä ollut sitä hänelle antamassa. Sinä olet niin
totinen, Jane. Tekeekö tämä sinut levottomaksi? Katsoisitko
mieluummin, että kantaisin leppymätöntä vihaa onnetonta kohtaan?»

»En, en, jatka. Sinähän olet antanut minulle sydämesi kokonaan,

jakamatonna; anna minun nähdä kaikki, mitä siinä on. Sinä et siis
kanna kaunaa uskottomalle?»

»En; minähän juuri tunnustin sinulle, että syytän itseäni

armottomuudesta. Nyt se on liian myöhäistä… Minä rakastan toista,
ja tätä toista ei kukaan voi ottaa minulta. Mutta tiedätkö, sinun
näkemisesi näyttääkin minulle uskottoman vaimoni lievemmässä
valossa… Sinä muistutat häntä kuin sisar… Mitä enemmän minä
katselen sinua, sitä selvemmin muistan nuo melkein unohtuneet
piirteet… sinun äänesikin on kuin kaiku kauan sitten soineista
sävelistä…»

»Hän on kuitenkin paljon rikkonut sinua vastaan?»

»Niin, silloin se tuotti minulle sanomatonta tuskaa… mutta voisinko

siitä enää olla vihainen? Mitä tuo lapsi raukka sitten teki? Oikeastaan
ei mitään pahempaa kuin me nyt. Hän ei rakastanut minua, enkä
minäkään rakastanut häntä niinkuin minun olisi pitänyt… mies, jota
hän seurasi, antoi kai hänelle oikean rakkauden… Mutta älkäämme
puhuko enää hänestä, puhukaamme mieluummin sinusta. Mitä sinä
oikeastaan tahdoit sanoa minulle!»

»Minä tahdoin sanoa sinulle, että voidakseni ottaa vastaan

rakkautesi täytyy minun tietää sen tarkoittavan yksin minua… vallan
yksin…»

»Voitko sitä epäillä?»

»Älä keskeytä minua. Minä tiedän Janen, johon kolme viikkoa

sitten tutustuit, saaneen sydämesi… mutta voidakseni olla onnellinen
sen omistaessani täytyy sinun tietää, kuka todellisuudessa olen…
Niin kauan kuin et tiedä menneisyydestäni, tuntuu minusta, kuin
esiintyisin naamarin takana, ikäänkuin sinä et rakastaisi minua, vaan
jotain toista, jonka osaa näyttelen… Minä en ole vielä sidottu
sinuun… vielä voin palata entisiin oloihini.»
 »Mitenkä voit puhua tuolla tavalla! Luuletko minun enää laskevan
sinua luotani? Huomenna me matkustamme täältä; muutamien
päivien kuluttua nousemme laivan kannelle matkataksemme uuteen
maailmaan, jossa perustamme kotimme, jota minä aina tulen
suojaamaan..»

»Se ei ole sanottu. Ellet sinä tunnustukseni jälkeen syleile minua

niinkuin minä tahdon, lähden minä vielä tänään takaisin
Wiesbadeniin… Kukaan ei saa tietoa tästä seikkailusta, ja meillä
kummallakin on vapautemme jälleen.»

»Ja tuota voit uskoa, Jane?… Tänä hetkenä voit luulla sen olevan
mahdollista?»

»Suoraan sanoen, en sitä pelkää. Mutta sinun täytyy kuunnella

minua…»

»Minkä vanhan synnin tahdot tunnustaa minulle? Mitä se

hyödyttää, Jane? Minä tunnen sinut ja rakastan sinua sellaisena kuin
nyt olet, huolimatta siitä, mimmoinen olet ollut. Paitsi että rakastan
sinua niin, että pyytäisin sinua tulemaan omakseni, vaikka olisit
rikoksentekijä, minä myös kunnioitan sinua. Sinähän olet menneinä
aikoina voinut hairahtua, mutta siitä, mitä nyt tunnet ja ajattelet, on
takeena koko olemuksesi. Ja sitäpaitsi maineesi, Jane. Sinä olet
kahdeksan vuotta oleskellut samalla paikkakunnalla, enkä ole
kenenkään kuullut puhuvan pahaa sinusta… ja äidillinen ystäväsi…
eikö sellaisen naisen ystävyys ole takeena arvostasi? Älä nyt huoli
kertoa mitään nuoruutesi harha-askeleesta. Minä voin jo tietää, mitä
tahdot minulle sanoa: sinähän olet jo viitannut siihen, että olet
jättänyt miehesi, jota et rakastanut… varmaankin seurataksesi toista
miestä. Älä herätä mustasukkaisuuttani kuvailemalla tätä sammuvaa
rakkautta… Hän kai ei sitä ansainnut?… Nyt sinä rakastat minua…
ja se on minulle kylliksi. Ja sinä olet rakastava minua aina, sillä minä
koetan ansaita sen…»

»Jospa tietäisit, miten hyvää sanasi tekevät minulle! Mutta kuule

minua sittenkin. Sinä olet arvannut mitä olen tahtonut tunnustaa
sinulle, nimittäin että kymmenen vuotta sitten hylkäsin mieheni
heittäytyäkseni toisen syliin…»

»Nyt kiusaa jo tuo pelkkä ajatuskin minua…»

»Mutta minä en koskaan ollut hänen omansa, Ewald. Hän kuoli

samana hetkenä, kun minä odotin häntä… Minä vannon sen
kaikkein pyhimmän, rakkautemme nimessä… Sinähän uskot minua,
kun katselen sinua näin silmiin?»

»Uskon, minä uskon sinua.»

»Ja sinä uskot, että nyt punastun häpeästä? Sinun

anteeksiantoasi tarvitsen, mutta en nykyhetkestä, vaan menneestä.
Ja minä luulen sinun antavan minulle anteeksi…»

»Rakas, miksi sinä vapiset?… miksi sinä itket?»

»En pelosta, en syyllisyydentunteesta. Kuten äsken vakuutin, en

ole kuulunut koskaan kenellekään muulle kuin miehelleni, ja sitä voin
viimeiseen hetkeeni saakka vakuuttaa, vaikka seuraisinkin sinua
maailman ääriin saakka ja olisin omasi…»

»Mitä sinä puhut?»

»Etkö ymmärrä minua, Ewald? Katsele minua… älä ajattele

tukkaani… katsele minua silmiin… etkö sinä tunne minua?»
 Hetkisen tuijotti Ewald häneen; sitten hän sulki hänet syliinsä ja
huudahti:

»Hanna, oma vaimoni!»

*****

Vasta seuraavana päivänä, kun Hanna istui miehensä kanssa

aamiaispöydässä, hän muisti saamansa kirjeen. Hän nousi ja otti
sen matkalaukustaan.

»Ewald, tämä on osoitettu meille molemmille», hän sanoi. »Se on

ystävältäni, ja hän pyysi, että me sovintomme jälkeen lukisimme se
yhdessä. Me kai olemme sopineet?» hän lisäsi nauraen.

»No noin puolittain», vastasi Ewald leikillisesti.

»Kas niin, lue nyt. Minä seuraan olkasi takaa.»

Ballmann mursi sinetin. Kuoressa oli laskostettu paperi. Sen hän

pani pöydälle ja luki ensin itse kirjeen:

»Rakkaat lapseni!

Kuuluisi kai asiaan, että kirjoittaisin nyt jotain hyvin surullista…

jonkun innokkaan hääpuheen, joka olisi teille parannukseksi. Mutta
minä olen itsekin niin iloinen, etten voi olla juhlallinen. Koska nyt
pidän itseäni morsiamen äitinä, tahdon myöskin olla osallisena
juhlassa ja lähetän teille häälahjan. Onhan luonnollista, etten anna
Janen, joka niin monta vuotta on ollut kuin oma tyttäreni, joutua
myynittä maailmalle. Mukanaseuraava paperipalanen on shekki,
jolla voitte nostaa neljäkymmentätuhatta puntaa eräästä Lontoon
pankista. Ostakaa niillä itsellenne maatila tai ilmalaiva tai mitä