main topic
Wien Med Wochenschr
DOI 10.1007/s10354-017-0553-7
The history of Botulinum toxin: from poison to beauty
Katlein França · Anagha Kumar · Massimo Fioranelli · Torello Lotti · Michael Tirant · Maria Grazia Roccia
Received: 10 November 2016 / Accepted: 14 February 2017
© Springer-Verlag Wien 2017
Summary Botulinum toxin, also called the “mira-
cle toxin,” is a neurotoxin produced by the bacteria
Clostridium botulinum. It is known to block nerve
signals that contract muscles resulting in a temporary
paralysis of the muscles. Toxins type A and B have
been extensively studied and utilized in the realm of
beauty and cosmetology. Initially, the toxin gained
popularity as a disease-causing “poison”. It was only
later that it found its way to becoming a must have in
modern aesthetic practice. Today, this wonder toxin
has proven to be an apt and convenient option in the
field of anti-aging medicine.
Keywords Botulinum toxin · History · Clostridium bo-
tulinum · Aesthetic · Remedy
K. França, MD, PhD · T. Lotti
Centro Studi per la Ricerca Multidisciplinare e Rigenerativa,
Università Degli Studi “G. Marconi”, Rome, Italy
K. França, MD, PhD ()
Department of Dermatology and Cutaneous Surgery,
Department of Psychiatry and Behavioral Sciences, Institute
for Bioethics and Health Policy, University of Miami Miller
School of Medicine, Miami, FL, USA
k.franca@med.miami.edu
A. Kumar
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine,
Miami, FL, USA
M. Fioranelli
Department of Nuclear Physics, Subnuclear and Radiation,
G. Marconi University, Rome, Italy
M. Tirant
Psoriasis and Skin Clinic, Melbourne, Australia
M. G. Roccia
University B.I.S. Group of Institutions, Punjab Technical
University, Punjab, India
K The history of Botulinum toxin: from poison to beauty
Botulinum toxin is a neurotoxin produced by the bac-
terium Clostridium botulinum. This neurotoxin is re-
sponsible for botulism, a dangerous form of food poi-
soning. Eight distinct serotypes (A, B, C1, C2, D, E,
F, and G) of the neurotoxin have been identified to
date [1]. Types A and B of the neurotoxin are known
to cause disease in man and they have been used
medically and therapeutically. The toxin is enclosed
in a molecular complex of hemagglutinins and non-
hemagglutinins and is released as a single chain from
the bacteria. It is then cleaved into a heavy chain
containing the binding domain for the synaptic termi-
nal and a light chain containing the metalloprotease
which is the active part of the toxin. At the synapse,
the toxin cleaves the Soluble NSF Attachment Protein
Receptor (SNARE) protein, thereby preventing the exit
of the toxin from the synaptic cleft. The toxin blocks
presynaptic acetylcholine release, thus, preventing the
nerve impulses responsible for muscle contraction.
Recovery from the toxin effect occurs by sprouting of
nerve terminals and formation of new synaptic clefts
[1].
Three main types of poisoning exist: food poison-
ing from the formed toxin (bacteria reproduce under
special conditions, namely a low-level or absence of
oxygen such as insufficiently heated canned products
and low acidity environments as in packaged coconut
water), infant botulism (where Clostridium botulinum
bacterial spores grow within a baby’s intestinal tract;
occurs between the ages of 2 months and 8 months,
leading to difficulty swallowing and breathing that can
be life-threatening. This is typically associated with
consumption of honey in infants), and in the form of
severe wound infections. Only recent research threw
light on how the toxin reached the blood stream from
the intestine. An accessory protein complex that dis-
rupts the cell adhesion in the intestines is formed,
thus, letting the toxin into the circulation.
 main topic
Table 1 Types of Botulinum toxin available in the United States
OnabotulinumtoxinA
Commercial names Botox®
Company Allergan Inc.
Units/vial 100/200
Strength (Botulinum 1:1
toxin A:product)
Storage before dilution 2–8
(in °C)
Storage after dilution 24 h
(at 2–8 °C)
Indications Blepharospasm, cervical
dystonia, glabellar lines, hyper- dystonia, glabellar lines
hidrosis, urinary incontinence,
chronic migraine
Botulinum toxin has been exploited widely in aes-
thetic practice to reduce glabellar lines, forehead
rhytids, crow’s feet, and perioral lip lines. Although
dermal fillers are best for nasolabial folds, Botulinum
toxin injection is an attractive option. The toxin is also
used to treat dimpled chin, platysmal bands, and also
popular for facial sculpting. Botulinum toxin prepa-
rations commercially available are constituted with
normal saline and the required dose is injected into
the target muscle. It is considered an office procedure
with minimal side effects like edema, erythema, and
pain at injection site. Headache, malaise, generalized
idiosyncratic reactions, and effects due to diffusion of
toxins to surrounding sites like dysphagia and ptosis
are rare. Dramatic results are seen within 3–4 days
and last around 3–4 months. Also, repeated injections
are known to be safe and yield superior results.
The units of Botulinum toxin A preparations are
not the same and doses are specific to each prepa-
ration. The difference in the units of Botulinum
toxin A preparations is due to differences in as-
say methodology, specifically the diluents. In the
United States, the commercially available prepara-
tions are Dysport® (abobotulinumtoxinA), Botox®
(onabotulinumtoxinA), Xeomin® (incobotulinumtox-
inA), and Neurobloc®/Myobloc® (rimabotulinumtox-
inB). Lasers, surgical facelifts, and dermal fillers are
other options that are more skill oriented and also ex-
pensive making Botulinum toxin injections extremely
doctor and patient friendly. Botulinum toxin injec-
tion is also being used as an adjunct to other cosmetic
procedures.
In the United States, different types of Botulinum
toxins are available on the market (Table 1).
The discovery of the toxin and its journey from be-
ing a dreaded biological substance to a cosmetologist’s
best friend has been a fascinating one. Not only has
it revolutionized the field of cosmetology, but it has
proven its versatility as being an effective remedy for
a wide range of disorders such as headaches, strabis-
mus, neck and limb spasticity, and urinary inconti-
nence.
The history of Botulinum toxin: from poison to beauty
AbobotulinumtoxinA IncobotulinumtoxinA RimabotulinumtoxinB
Dysport® Xeomin® Neurobloc®/Myobloc®
Ipsen Merz Pharmaceuticals Solstice Neurosciences Inc.
300/500 50/100 2500/5000/10,000
1.2–1.4:1 1:1 1:50–1:100
2–8 2–8 2–8
4h 24 h 4h
Blepharospasm, cervical Blepharospasm, cervical Cervical dystonia
dystonia, glabellar lines
The history of the botulinum toxin has been long,
interesting, and illustrious. Botulinum toxin poison-
ing seems to have affected mankind since time im-
memorial. With civilization, there were early attempts
to safely keep and preserve food, leading to the organ-
ism possibly thriving on human food stores. Indian
history shows that the Maharajas used “poison” ex-
tracted from sausages to kill enemies.
The first historical description of botulism dates
to 1735, and in 1793, in Germany, several persons
died after eating uncooked blood sausages [2, 3]. Ini-
tially it was suspected to be Atropa belladonna poi-
soning but soon that theory was discarded. It was
concluded that the consumption of “Blunzen” a pop-
ular local food made of pork stomach filled with blood
and spices was the cause of this food poisoning. In
1802, the local government in South Western Ger-
many issued a public notice regarding the harmful
consumption of blood-filled sausages. Professor Aut-
enrieth, University of Tubingen, made the first at-
tempt to analyze the symptoms of these cases of food
poisoning. The German physician Justinus Christian
Kerner (1786–1862) was the first to study botulism
and named the new toxin “sausage poison”. But he
failed in defining the suspected “biological poison”
[3]. In 1895, Emile Van Ermengem (1851–1932), Pro-
fessor of Bacteriology at the University of Ghent, iso-
lated the bacterium Clostridium botulinum. He had
obtained the samples from a piece of ham that had
poisoned people at a funeral dinner in the Belgian vil-
lage of Ellezelles [4, 5]. He isolated the same organism
from the ham and in the corpses of the victims. He
named the toxin “Bacillus Botulinus”, the word “Botu-
lus” meaning sausage in Latin. This milestone discov-
ery also yielded precious clinical information about
the disease. It was concluded that Botulism is a poi-
son rather than an infection and that there was no
toxin production in the presence of salt and that the
toxin could be inactivated by heat.
By the early twentieth century, the food canning in-
dustry was booming and with it the risk of botulinum
poisoning increased. There was a need to control the
new “food poisoning” epidemic. It was then that the
K

Swiss–American scientist Karl Friedrich Meyer discov-
ered techniques to prevent growth of the organism by
inactivating the toxin by heat. It was only in 1944 that
the biochemist Edward Schantz (1908–2005) cultured
Clostridium botulinum and isolated the toxin. In ad-
dition, different serotypes of the toxins were subse-
quently discovered.
But it was in 1949 that Burgen’s group discovered
that Botulinum toxin blocks neuromuscular trans-
mission [5]. This neurotoxin is so poisonous that in
humans, the LD50 is estimated to be just 1.3–2 ng/kg
through Intramuscular/Intravenous routes and
10–13 ng/kg when inhaled. Known to be the most
poisonous substance known during that time, failed
efforts were made to exploit Botulinum toxin in bi-
ological warfare during World War II. Research from
Carl Lamanna and James Duff led to the discovery of
the concentration and crystallization techniques of
the toxin [6].
It took three to four decades until the deadly toxin
could be used therapeutically. It was utilized in hu-
mans only in 1980, by the ophthalmologist Alan B
Scott, to treat strabismus. Almost 10 years later,
in December of 1989, the US Food and Drug Ad-
ministration (FDA) approved onabotulinumtoxinA
(Botox®) for treatment of strabismus, blepharospasm,
and hemifacial spasm in children younger than age
12 years. In 2000, FDA approved its use for cervical
dystonia.
It was in 2002 that the FDA approved it for cosmetic
use, to improve the appearance of glabellar lines. Two
years later, in July 2004, it was accepted to treat axil-
lary hyperhidrosis. In 2010, it was approved to treat
adults with chronic migraine and then in 2011 for uri-
nary incontinence associated with neurological con-
ditions. In 2013, the FDA accepted it for the treatment
of lateral canthal lines (crow’s feet) making it the only
FDA approved remedy for the condition. Botox is also
an off-label remedy for eye brow lift, gummy smile,
depression, and even temporomandibular joint disor-
ders. Botulinum toxin B (MyoBloc®) was approved for
the treatment of cervical dystonia in 2000. Dysport®
and Xeomin® were most recently approved in 2015 to
treat upper limb spasticity.
K The history of Botulinum toxin: from poison to beauty
main topic
Botulinum toxin injection is the most commonly
performed nonsurgical cosmetic procedure performed
in the US. Compared to other anti-aging procedures
like lasers, surgical procedures, and fillers, it is less
invasive, easier to perform and quicker procedure
also yielding relatively immediate and dramatic re-
sults [7]. It is suggested that with these advantages it
could replace other invasive facial procedures [8]. The
Botulinum toxin industry is projected to have sales
worth billions of dollars in the next few years. It is
constantly being evaluated for new uses in the fields
of cosmetology and medicine.
The Swiss Physician Paracelsus’s statement “All sub-
stances are poisons, there is none that is not a poison.
The right dose differentiates a poison from a remedy.”
suits well for botulinum toxin.
Conflict of interest K. França, A. Kumar, M. Fioranelli,
T. Lotti, M. Tirant, and M.G. Roccia declare that they have
no competing interests.
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