the immune system can recognize and
subdue. In other cells, though, it remains
dormant. ‘‘It’s very stealthy,’’ Cohen says.
Ultimately, as those infected B cells circu-
late throughout the body, they reach the
back of the throat again. The virus awak-
ens and starts producing proteins, which
its host sheds, potentially spreading the
pathogen to others, probably for sever-
al days each month. ‘‘The vast majority
of people who are infected are passing
it around,’’ Cohen says. ‘‘It’s shed in our
saliva the rest of our lives.’’
Scientists have long hypothesized
that viruses, including Epstein-Barr, are
involved in the development of autoim-
mune diseases, in which the immune
system mistakenly attacks healthy tis-
sue. Evidence links it to lupus, and a
recent study reported that people with
long Covid were more likely than oth-
ers to have an active Epstein-Barr infec-
tion (though it is unclear whether that
infection causes symptoms, because the
virus can proliferate when the immune
system is under stress without creating
any health problems). There are docu-
mented associations between mono and
multiple sclerosis, a disease in which the
immune system destroys a protective
sheath called myelin that coats nerve
fi bers, often disabling communication
between the nervous system and the rest
of the body. ‘‘People have been trying
for many, many decades to prove that a
virus causes M.S. or rheumatoid arthri-
tis,’’ says William H. Robinson, the chief
of the immunology and rheumatology
division at Stanford. ‘‘And they have not
been able to convincingly demonstrate
that it does.’’
The very ubiquity of Epstein-Barr has
made it especially diffi cult to isolate as
a causal factor. To show that Epstein-
Barr causes M.S., or any other condition
that takes years to develop, researchers
would need to fi nd a group of people
who don’t have the virus and follow them
over decades to see who becomes infect-
ed — and of those, how many go on to
develop M.S., compared with how many
without Epstein-Barr do. Such a study
would need tens of thousands of partic-
ipants, because only about 10 percent of
the adult population has not been infect-
ed by Epstein-Barr by their mid-20s, and
an even smaller number of people — 1 in
330 in the U.S. — develop M.S., usually
between age 20 and 50.
Researchers from the Harvard T. H.
Chan School of Public Health and else-
where, however, devised a novel way to
carry out that study, and they published
their fi ndings in January in Science. U.S.
military recruits, a group of more than
10 million people, are screened for H.I.V.
when their service starts and biennially
thereafter. Their blood serum samples
are then archived in the Department of
Defense Serum Repository and can be
retested for other pathogens. Between
1993 and 2013, the researchers identifi ed
cases of M.S. among active-duty U.S. mili-
tary personnel. Then they tested their fi rst
serum sample; their last sample before
M.S. onset; and one in between. They
found that of 801 soldiers with M.S., 800
were positive for Epstein-Barr.
They also looked at serum samples
from a randomly selected group of those
participants’ peers with similar charac-
teristics, such as age, gender, race and
branch of service. At the time of the fi rst
sample, 35 of the M.S. cases tested nega-
tive for the virus and 107 of the controls
did. By the last test, all but one of the M.S.
cases were positive for the virus, whereas
only 57 percent of those who didn’t have
M.S. were. ‘‘In practical terms, if you’re
not infected with E.B.V., your risk of M.S.
is virtually zero,’’ says Alberto Ascherio,
a professor of epidemiology and nutri-
tion at Harvard and a senior author of the
Science study. ‘‘After infection, your riskjumps by over 30-fold.’’ The odds of that
increase having occurred by chance are
less than one in a million.
That was the strongest evidence yet
that Epstein-Barr initiates M.S., but it
didn’t explain why. Just over a week after
the Science paper came out, though, Rob-
inson and colleagues published their own
paper in Nature that demonstrated how
the virus triggers the disease in some
people. Epstein-Barr produces proteins
that mimic a protein in the myelin sheath,
they found; when the immune system
makes antibodies to attack the virus, they
also attack the myelin — ‘‘the insulation
around your neurons,’’ as Robinson puts
it. ‘‘Like electrical wires, if the insulation
gets stripped off , it short- circuits,’’ he says.
‘‘That’s what results in M.S.’’
This protein mix-up, though, can only
explain about a quarter of M.S. cases.
And while the Science paper concludes
that Epstein-Barr is the ‘‘leading cause’’
of M.S., Cohen says he wants to be care-
ful with the word ‘‘cause.’’ He thinks the
study proves that the virus is a necessary
precondition for M.S., but the fact that
so many people have Epstein-Barr and so
few of them get M.S. demonstrates that
other factors, very likely including genet-
ic susceptibility, must play a signifi cant
role in the development of the disease.
Still, similar hard-to-disentangle circum-
stances describe other diseases for which
most people do feel comfortable pointing
to a specifi c culprit. The C.D.C. refers to
polio as ‘‘a disabling and life-threatening
disease caused by the poliovirus,’’ for
instance, but fewer than fi ve in a thousand
people who contract the virus develop
serious symptoms.
What is exciting about the discovery
that Epstein-Barr is necessary for M.S. is
that it raises the prospect that a vaccine
could prevent that disease — as well as
other serious conditions — even if we
never understand precisely why the virus
behaves as it does in a given individual. As
long as the link between Epstein-Barr and
M.S. remained controversial, commercial
and popular interest in such a vaccine was
‘‘lukewarm,’’ says Hank Balfour, a profes-
sor of laboratory medicine, pathology and
pediatrics at the University of Minnesota
Medical School and the principal investi-
gator of the Mono Project, an Epstein-Barr
disease research group that hopes to begin
clinical trials of a vaccine this year. ‘‘Now I
think things will change.’’Kim Tingley
is a contributing writer
for the magazine.Studies Show
16 2.27.22 Illustration by Andrea Ucini