Achievement: For
pioneeringcontributions
research contributing
to theAchievement: For
outstanding
to estimation
ofof mRNA
vaccines
global biosphericdevelopment
productivity andclimatechange science
using advanced formulas based on observation
Prof. Katalin Karikó (Hungary/ USA)
(Age: 67)
Born:Christopher
January 17, 1955Field
Prof.
(USA)
SeniorVice12,President,
BioNTech
Born:March
1953 (Age:68) SE
Director,
Institutefor theEnvironment,
Stanford
University
AdjunctWoods
Professor,
Perelman
Schoolof Medicine,
Universityof Pennsylvania
Professor
forUniversity
Interdisciplinary
Environmental Studies
Professor,of SzegedProf.
Drew
Weissman and(USA)Measuring
photosynthetictranspiration rates

Born:
Septemberof living
leaves 7, 1959 (Age: 62)
Professor of Medicine, University of Pennsylvania School of Medicine
Director Penn Institute for RNA Innovation
Plants absorb CO2 in the atmosphere through photosynthesis and convert it
into organic matter. However, a great variety of plants can be found on Earth,and the photosynthetic rate of each plant depends on the climate, the soil, its
altitude, and other factors particular to the environment in which it grows.
InThethe role
early of1980s,Fielda device that could measure bothmRNAin developed
protein synthesis
photosynthetic and transpiration rates of leaves (see photos below). It allowed
for thecontrol areof temperature,humidity,andimmune
CO2 concentration
to measure
Vaccines
medicines that
remind thesystem to attack
proteins
particular to specificpathogensrates
in orderto gainimmunityresistance) tophotosynthetic
and transpirationof leavesundervarious(i.e.,conditions.
external
suchaspect
as viruses
andbacteria.
The mostpathogens
advantageousof thisdevice
was its portability. Without that,human cellsby attaching
to them using
proteins
plantsCOVID-19
would haveinfects
to be gathered
and brought
to a laboratory,
whichspike
affectedthe(the red, club-shaped elements seen in Figure 1.) Previous coronavirus
environment and biological activity, and therefore resulted in inaccurate data.
research has shown that fragments of those spike proteins can act as antigens
Thisactivate
device theenabledresearchers
to produce
analyze plants
in-situ using the “livingandimmune
system toantibodies.
leaves”
ofplants
rootedinthesoil.
Theycould
thengather
real
The problem with using spike proteins in vaccines is
how togetdatathemthat
intoreflected
theItgrowing
environment,
as themtheredirectly,
was no longer
any withneedconventionto collectthe body.
is possible
to administer
as is done
vaccines,
but mRNA vaccines harness mRNA, which serves as a blueprint
oralmovethe plants.
forcellsbrought
to synthesize
spiketoproteins,which
can bea synthesized
Field
the device
various andareas
to gathervast amountartificiallyof data
beforehis
being
duringfieldadministered.
surveys and experiments.
Our bodies know which proteins to make by using our genetic blueprint orEquipment
usedto measureon
photosynthetictranspirationof livingleaves.
DNA. Theinformation
DNA neededrate
forandproteinsynthesis
is copied
overto the mRNA, whereupon the ribosomes in the cells read that information
and begin synthesizing protein. This biological function is used to effectively
produce spike proteins within the body.

How the COVID-19 vaccine works

Analyzing a living plant leaf in soil.

The equipment can all be stored
in a carrying case.

What mechanisms do COVID-19
vaccines
harness
prevent viral
Field et al. (1982,Plant,
Cell &toEnvironment)
infection and reduce symptom severity?
First, vaccination allows the spike protein-coded mRNA to enter theLeafThat
photosynthesis
andstomaticbody.
mRNA uses thebody’s
proteinfunction
synthesis ability to produce spike
proteins. Since these proteins are recognized as coming from outside of thebody,alsoareknown
as “non-self”
theofimmune
systemactivated
Stomatatiny poresfound on proteins,
the surface
plant leaves,andisstomatal
resistance is used to describe how easily CO2 and water vapor pass throughFigure 1: The role of mRNA in protein synthesisFigure 1: Relationship between photosynthetic rate,
leaf nitrogencontent and light intensity
Virus genetic
Spike protein
information
Leaf nitrogen content(blueprint)
COVID-19

Net photosynthetic rate (µmol CO2/g/s)

１

Field ofof Materials
andProduction,
Production Ecology/Environment
Field
Biological

60

0.3

40

Synthesized mRNA

0.2

20

0.1

Resulting protein is folded
into the10spike protein0

Ribosome

0

Ribosomes produce proteins(inside the cell)

0.5
1.0
1.5
2.0
Light intensity (mmol/m2/s)

Spike Proteins

Based on Field (1983, Oecologia)

produceofantibodies(left image inField’sFig. 2).
Once thesystem has A
thetostomata
a leaf. By incorporating
formulasforimmune
photosynthesis,
made a recordof spike
proteins,
COVID-19
enter
the body,
a rapid in
it becamepossibleto estimate
the ifflowof CO2 virions
and water
vapor
betweenimmuneresponse
is induced (right image in Fig. 2).
plantsand theatmosphere.
Vaccines were conventionally made using attenuated versions of aField continued to engage in theoretical research based in the data hevirus or even the viral pathogens themselves, so it took time to guarantee a F
gatheredin safety,
his field
and experiments.
He madetowou
vaccine’si.e.,surveys
to guaranteethat the vaccine
woulditnotpossible
cause illness,
describe
complexplant
phenomenainaquantitativewaybyexpressing
and to confirm its effectiveness in granting immunity to the disease being wou
photosynthetic
leaveshand,throughfunctionproductionthat dependsofonspike
temperature,targeted. Onrate
theinotherthe ainduced
proteins in A
the atmosphericbody involves
use of an actual
so there
nootherrisk ofinfection, CO2
light,
COno2 concentration,
leafvirus,nitrogenlevel, isandfactors.
andthe antigenic
efficiency ofinfluence
spike proteinscan be easily shown,so such that
Nitrogenhas a significant
on photosynthesis
rate. Field
vaccineshow
can photosynthesis
be made highly effective.
revealed
rate depends on leaf nitrogen content
to yThis is the basic mechanism through which the mRNA COVID-19 vaccine
and irradiance levels (see Fig. 1). This research has also contributed tostabworks.
agricultural efforts to improve the efficiency of nitrogen fertilizers.
thatField’s formulas were introduced into the climate models essential tother
understanding and predicting climate change caused by global warming.
T
Paving the way to mRNA drugs with pseudouridine
CO2 is extracted from the atmosphere through the opening and closing
is aof the stomata, and water vapor drawn up from the roots is also releasedcon
The reason
why mRNA had not been used in pharmaceutical products was(see Fig.
2).
atm
because it degrades quickly in vivo and, particularly when administered fromField’s equations were introduced into climate models, and with theoutside the body, it is recognized as abnormal by the body thereby triggering emi
additionof living plants,
carbon As
cycle– i.e. cells
the interchange
an inflammatory
immunetheresponse.
a result,
administeredand
withflowmRNA andof wereCO2 dying
betweenplantsandtheatmosphere
andoceans–
becamebefore they could produce the amount of protein neededatonew
acquire F
partof the climate
models.
immunity,and vaccines
were causing fevers and other issues in recipients. dev
Professors
Karikó
and Drew
Weissmanbegan
Thismade itKatalin
possibleto answer
questionssuchas collaborating
how the riseinin1998 CO
when they wereat the Perelman
School of Medicine
at thegrowth
University andatmospheric
CO2 bothconcentrationand temperature
affects plantof photosynthesis
Pennsylvania inrates,
the andhopesof conducting
research
the potential
andwhat
sort of feedbacks
areintoproduced.
That of imp
harnessing mRNA in drug creation. In 2005, they discovered that they could
understanding led to the ability to predict future climate change throughlook at mRNA as a single substance, and that they could replace its constituent
understanding
CO2 cycle.
uridine with athemodifiedversion called pseudouridine, thereby suppressing anyFigu
undesired immune response (see Fig. 3).
At the time, it was known that immune response can be caused when NmRNA introduced from outside the body binds to Toll-like receptors on the 6
COmembrane,
thenotglobalbiosphere
2 absorption
cell
but init wasyet known
that this binding occurs by way ofuridine. After repeated experimentation, Karikó and Weissman learned that 3mRNA
pseudouridine
doesupon
not bindto those receptors.
Field’swith
formulasare basedobservationaldata, and wereEdeveloped to treat plant ecosystems as a single, virtual leaf. Gaining
a qualitative understanding of the environmental response of complex－3
After throughyears ofthesemRNA
research
relatedbecause
technologicalvegetation
formulaswas andsignificant
it broadened－6
development,a vaccineis born
the applicabilityof theanalyticalmodel to cover both terrestrial vegetation and marine biospheres.
SmRNA vaccine
to have appeared
all ofsudden,and
but inInThecollaboration
with may
Earthseem
observation
researchers
at aNASA
reality,mRNA firstField
beganto beconsidered
use in medicalsatellites
applications
otherorganizations,
used
data
gathered forby observational
more
than30years
ago.
Researchhas
continued
sincethen,even
to estimate how much CO2 is being absorbed by which vegetation –thoughi.e. it
did not lead to development of any drugs. It wasn’t until 2020 and the urgent
plant photosynthetic productivity – around the planet.
need presented by the COVID-19 pandemic arrived that a practical mRNAIn addition,by collaborating
vaccinewas successfully
made.with marine researchers and integrating
their Bolstering
data from marine
biospheres,
he wasable to create
the mRNA
first global
the seemingly
short-term
developmentof thevaccine FCO
2 absorption
and emission
wasthe accumulated
wisdom distributionof the entiremap
bodythatof included
molecular bothbiologyterrestrial and marine ecosystems (see Fig.3 map).

Figure 2：How the COVID-19 vaccine works

mRNA is placed in tiny,
Figure 2: Leaf photosynthesis
and capsule,stomaticand
function
specially-madeadministered as an injection

Stomatal resistancemeasures how easily
CO2 and water vapormRNA
Sensible pass through theheatPAR
stomata of a leaf. ByATP, NADPH
Water
incorporating Field’svapor
CalvinStomatal resistanceformulas for photosynLight
cycle CO2
CO2reactions
Spike proteinsthesis, it became
O2Antibodies
possible to estimate theH2O
flow of CO2 and water
PhotosynthatemRNA degradesfrom Soil（C6H12O6 etc）
vapor between plants
quickly without
Illness cannot be caused
accumulating
and the atmosphere.
only by spike proteinsin the body

Stem androots

Leaf interior

Stomate\Leaf boundary
COVID-19

Based on Sellers et al. (1997, Science)

Spike proteins produce
antibodies to combat virus

Antibodies are produced rapidly,
helping prevent severe symptoms

e inwth
Thatughwerening
plex
nedeta-and
ites
i.e.

tingobalbothn-thers－60
SPHow
COVID-19
vaccine 0works 60°E
180 the120°W
60°W

120°E

Low

180

High

Pole, Eq vaccines= Equator, SP= SouthtoPole)
2 Absorption (NP=North
WhatCOmechanisms
do COVID-19
harness
prevent viral
infection and reduce symptom severity? Field et al. (1998, Science)First, vaccination allows the spike protein-coded mRNA to enter thebody. That mRNA uses the body’s protein synthesis ability to produce spikeproteins. Since these proteins are recognized as coming from outside of theFigure 4: Artificial CO2 emissions and environmental CO2 absorption
body,also known as “non-self” proteins, the immune system is activated33

Figure 1: Theroleofuse
mRNA in protein synthesis
land86

fossil fuelland use

Virus genetic

246

Synthesized mRNA
atmosphere
11

Resulting protein is folded into theland
spike protein
ocean

atmosphere
Ribosomeland
8
Ribosomes produce proteins
Ocean(inside the cell)

1960

1970

1980

Spike Proteins time (y)1990

The reason why mRNA had not been used in pharmaceutical products wasbecause it degrades quickly in vivo and, particularly when administered fromoutside the body, it is recognized as abnormal by the body thereby triggering
an inflammatory immune response. As a result, cells administered with mRNA
were dying before they could produce the amount of protein needed to acquire
immunity, and vaccines were causing fevers and other issues in recipients.
Professors Katalin Karikó and Drew Weissman began collaborating in 1998
when they were both at the Perelman School of Medicine at the Universityof Pennsylvania in the hopes of conducting research into the potential ofharnessing mRNA in drug creation. In 2005, they discovered that they could
look at mRNA as a single substance, and that they could replace its constituent
uridine with a modified version called pseudouridine, thereby suppressing any
undesired immune response (see Fig. 3).
At the time, it was known that immune response can be caused whenmRNA introduced from outside the body binds to Toll-like receptors on thecell membrane, but it was not yet known that this binding occurs by way ofuridine. After repeated experimentation, Karikó and Weissman learned thatmRNA with pseudouridine does not bind to those receptors.

After years of mRNA research and related technologicaldevelopment, a vaccine is born
The mRNA vaccine may seem to have appeared all of a sudden, but inreality, mRNA first began to be considered for use in medical applications
more than 30 years ago. Research has continued since then, even though it
did not lead to development of any drugs. It wasn’t until 2020 and the urgent
need presented by the COVID-19 pandemic arrived that a practical mRNA
vaccine was successfully made.
Bolstering the seemingly short-term development of the mRNA vaccine
was the accumulated wisdom of the entire body of molecular biology

11(blueprint) fossil fuel combustion
COVID-19

2Paving the way to mRNA drugs with pseudouridine

mRNA is placed in tiny,
specially-made capsule, andadministered as an injection

22Spikeprotein
other emissions

4 information

to produce antibodies (left image in Fig. 2). Once the immune system has
made a record of spike proteins, if COVID-19 virions enter the body, a rapid
immune response is induced (right image in Fig. 2).
Vaccines were conventionally made using attenuated versions of avirus or even the viral pathogens themselves, so it took time to guarantee a
vaccine’s safety, i.e., to guarantee that the vaccine would not cause illness,and to confirm its effectiveness in granting immunity to the disease being
targeted. On the other hand, the induced production of spike proteins in
the body involves no use of an actual virus, so there is no risk of infection,and the antigenic efficiency of spike proteins can be easily shown, so such
vaccines can be made highly effective.
This is the basic mechanism through which the mRNA COVID-19 vaccineworks.

Figure 2：How the COVID-19 vaccine works

2000

COVID-19
CO2 ﬂux(PgCO2/y)thelownew

sourcesal toing.
sing
ased

Achievement : For pioneering research contributing to thedevelopmentof mRNA
vaccines produced CO2
Field was also able
to estimate howmuch artificiallywouldabsorbed Karikó
by land and(Hungary/marine ecosystems,
and how much
Prof.beKatalinUSA)
wouldthe1955
atmosphere(see chart in Fig. 4).
(Age: 67)
Born: remain
Januaryin17,Artificial
2 emissions
are rising
SeniorVice COPresident,
BioNTechSE every year, and the amount ofAdjunct
Professor,
Perelman
Medicine, University
PennsylvaniaCO
2 absorbed
by oceans
is Schoolrising ofaccordingly,
but Field ofdiscovered
Professor,
University
Szeged vegetation fluctuates wildly from year
that
CO2 absorbed
by ofterrestrial
to year. It was thought that CO2 was absorbed by land vegetation in aProf. Drew Weissman (USA)stable way, but that turned out not to be the case. His estimation showed
Born: September 7, 1959 (Age: 62)
thatany CO
not absorbedon land ofremains
in the atmosphere,
and isProfessorof2 Medicine,
UniversityPennsylvania
School of Medicine
therebyresponsible
for theofInnovation
atmospheric CO2 concentration.
DirectorPenn Institutefor riseRNA
Through his research, Field has been able to show how much CO2
is absorbed by marine and terrestrial ecosystems as global warming
continues unabated, and to show how many years it will take to reduce
atmospheric CO2 concentration if humanity is able to reduce its CO2The rolemRNA
in protein
emissionsandoflimit
deforestation
andsynthesis
other related changes in land use
and land cover.
Vaccines
are medicines
the immune ofsystem
to attackField’s
researchbegan thatwithremindthe observationa single
leafproteinsandparticulartospecific
pathogensinorder
togainimmunity(i.e.,resistance)developed into a way to study global biospheric productivity using toexternalpathogens such as viruses and bacteria.
CO
2 emissions, contributing immensely to the study of climate change,
COVID-19 infects human cells by attaching to them using spike proteins
and laying the scientific foundation for international discussions to(the red, club-shaped elements seen in Figure 1.) Previous coronavirus
implementtheshown
measuresneeded toofcombat
globalwarming.
research hasthat fragments
those spike
proteins
can act as antigens
and activate the immune system to produce antibodies.
The problem with using spike proteins in vaccines is how to get them into
Figure3: Distribution
in the global
biosphere
2 absorption
the body.
It is possible ofto CO
administerthem directly,
as is donewith conventionalNP
vaccines, but mRNA vaccines harness mRNA, which serves as a blueprint
for cells to synthesize spike proteins, and which can be synthesized artificially60
before being administered.
Our bodies know which proteins to make by using our genetic blueprint or30
DNA. The information on DNA needed for protein synthesis is copied overtoEqthe mRNA, whereupon the ribosomes in the cells read that information
and begin synthesizing protein. This biological function is used to effectively－30
produce spike proteins within the body.

sinksa hee tosingure,ors.
ieldtentd toArtificial
CO2 emissions
and CO2 absorption
Field of Materials
and Productionin the environment

CO2 ﬂux(PgC/y)esis,
weenmRNA

Spike proteins

22Antibodies

33

Illness cannot be caused
only by spike proteinsmRNA degrades
quickly without
accumulatingin the body

Spike proteins produce

Based on Canadell et al. (2007, PNAS)antibodies to combat virus

Antibodies are produced rapidly,
helping prevent severe symptoms