Report, 1997, Utrecht University and Wageningen
Agricultural University, The Netherlands
Fetal bovine serum (FBS) is the most widely used serum
in the culturing of cells, tissues and organs in vitro, in industry,
medicine, and science. It can be used for nearly every cell type.
Countries which harbour facilities involved in fetal blood harvest for
(commercial) FBS production include: Canada, the USA, Honduras,
Venezuela, Brazil, Uruguay, Argentina, Chile, South Africa, France,
Sweden, Hungary, Estland, Lithuania, Letland, the Czech Republic,
Slovakia, Australia, New Zealand, probably Mexico, probably Paraguay,
would include Russia, possibly Spain, possibly Namibia - Botswana -
Zimbabwe.
Bovine fetuses used for FBS harvest come available from
extensively kept meat cattle (herds are always sent to slaughter in
their entirety, whether or not cows are pregnant is not determined),
from pregnant cattle sent to slaughter for reasons of unavoidable
culling (e.g. due to accident resulting in crippleness), and possibly
from cattle which are deliberately made pregnant for the production of
FBS. The latter would take / have taken place in Hungary, the Baltic
States, and possibly in the Czech Republic and Slovakia. In all other
countries -- except Honduras - fetuses are derived from pregnant meat
cattle. In Honduras, fetuses would only be derived from pregnant cull
cows. In the USA fetuses are derived both from pregnant meat cattle and
cull cows. Countries which do explicitly not harbour facilities in which
fetal blood is harvested for (commercial) FBS production include:
Iceland, Norway, Finland, Denmark, the Republic of Ireland, the United
Kingdom, The Netherlands, Germany, Austria, Switzerland, Portugal,
Italy, Greece, Slovenia, Croatia. Countries not mentioned above have not
been investigated. The mondial supply of raw FBS would be approximately
500,000 litre's per annum.
When during evisceration of the mother bovine as part of
the regular slaughter procedure, a fetus is discovered, it may be used
for FBS harvest. The blood from bovine fetuses which are used for FBS
production is usually obtained by means of a cardiac puncture (all
countries mentioned above, except Uruguay); alternatively, it may be
harvested by means of umbilical vein puncture (Uruguay, Australia), or
puncture of the jugular vein (Brazil). A cardiac puncture is the method
of preference for septical reasons. The fetal heart must still be
beating in order to harvest blood for FBS production purposes by means
of cardiac or umbilical cord puncture, in order to pump the blood
outside the body.
The time that elapses between death of the mother bovine
on the slaughter line, and the performance of a cardiac or umbilical
cord puncture is stated to be � 5 minutes (Chile, serum harvesting
company; Brazil, serum harvesting company; USA, former USDA inspector)
and � 25-30 minutes (Australia, serum harvesting companies and relevant
authority; New Zealand, relevant authority; South Africa, harvesting
company; Sweden, relevant authority). Note that authorities get their
information from the companies involved in harvesting. The term of 25-30
minutes may be doubted however, as this statement was usually
accompanied by the information that the fetal heart would not function
at the time of cardiac puncture and the fetus would be dead. It was
argued that the fetus dies at approximately the same time as does the
mother. This does not seem probable, as fetuses and neonates of mammals
are remarkably resistant to lack of oxygen supply.
A bovine fetus never receives anesthesia prior to a
bleeding procedure. Mammal fetuses can feel pain, depending on the
maturity of the nervous system. Bovine fetuses used for FBS harvest are
usually at least 6 months of gestational age, though fetuses may be used
as soon as 3 months gestation. Pain may be felt at the cortical level,
and in the absence of a functional cortex, in the thalamus. Moreover,
the pain threshold increases gradually during life, i.e. fetuses are
more vulnerable to pain than are neonates, which are more vulnerable to
pain than adults. The assessment of the extent of discomfort a bovine
fetus endures as a result of a bleeding procedure is hampered by the
lack of oxygen in the fetus at the moment of bleeding. Lack of oxygen
(anoxia), probably interferes with pain sensation. Moreover, cerebral
anoxia is a common means of inducing unconsciousness in animals
postpartum. The resistance of a mammal fetus to lack of oxygen increases
with decreasing gestational age. As there are too many variables which
influence the fetal physiologic state (e.g. maternal pre-slaughter
stress, effects of hypoxia like redistribution of blood flows to the
brain (brain stem), heart (myocardium), and adrenals (catecholamine
production), maturity at the moment of bleeding) it is not possible to
explicitly quantify the amount of discomfort in the fetus associated
with a bleeding procedure. Altogether, considering the high severity in
adults of exsanguination in itself, and a cardiac puncture in itself, it
is stated that it cannot be excluded that a bovine fetus of the
appropriate gestational age (3-4 months), used for FBS harvest by means
of cardiac or umbilical cord puncture, experiences low, moderate, or
(very) severe pain or suffering from the bleeding procedure. Therefore,
it may be suggested to destruct the fetal brain prior to the performance
of a cardiac or umbilical cord puncture by means of a penetrative
captive bolt, what can be considered a form of euthanasia.
However, a bovine fetus is currently never exposed to
any technique rendering it insensible to noxious stimuli prior to
bleeding. It remains to be seen if this will happen in the short future.
Thus, an ethical problem exists which is related to the use of FBS. The
fact that the fetus may endure pain or suffering from a bleeding
technique affects the niche which in vitro techniques currently occupy
as an alternative in animal experimentation. Additionally, many cells,
tissues or organs cultured in vitro for research or production purposes
are derived from animals which were killed for the purpose of obtaining
these materials. Animals which are killed for the purpose of obtaining
their cells, tissues or organs are considered experimental animals
according to animal experimentation legislation in many countries.
The ethical problem related to FBS is not the only
concern related to its use for the culturing of cells, tissues or organs
in vitro. Worries over its costs, availability, quality (contamination,
support of cell growth), imprecise molecular composition (batch-to-batch
variation) and ethical quality stimulate the search for methods to
culture cells without FBS. A final concern might involve the
malpractices reported in FBS trade. The consumer may be saddled with a
product which is not of the geographical origin he desired (e.g. there
seems to be more 'New Zealand' labeled FBS available than is harvested
there). Other (incidental?) malpractices include the diluting of New
Zealand FBS with FBS from a cheaper geographical origin, and supplying
FBS from countries which do not have facilities in which FBS is
harvested (including Finland, the UK, the Republic of Ireland, The
Netherlands, Denmark, Switzerland, and part of the French-originating
FBS). The true geographical origins of these sera have a less favourable
bovine disease status than e.g. Finland. The disease status of the
geographical origin determines the price of the serum for the consumer.
Selling a product as being of a geographical origin it is not of, is an
offense of Dutch Law.
Cells, tissues or organs can be cultured in vitro in the
absence of FBS. However, the cell type(s) concerned determine the
optimum serum (substitute) and concentration. Substitutes for FBS
include synthetic media (cell type specific), and reduced-serum media
(broader applicability then synthetic media). Fetal horse and fetal pig
serum cannot be considered FBS alternatives on ethical grounds, as they
are also usually harvested by cardiac puncture. Otherwise, cells can be
cultured in the presence of culture medium containing sera from newborn
calves (NCS), donor livestock, and sera obtained at slaughter from
non-donor animals. Finally, cells can be cultured properly in the
presence of culture medium containing a specific fraction of bovine
colostrum. The altered compositions of FBS substitutes may influence
cell characteristics, and suggests that certain in vitro experiments
would have to be redone after having switched to an FBS substitute. From
an ethical point of view, the use of NCS is not recommendable as a
substitute for FBS. New Zealand NCS is ethically disputable because of
the adverse side effects for both calf and mother animal related to
induction of parturition. Mishandling of newborn calves has been
reported from Mexico, Hungary and Brazil. Concerns over this issue
remain.
Therewith, the use of NCS as a substitute for FBS does
not seem recommendable, unless beyond doubt from a geographical origin
where proper newborn calf treatment would be assured (e.g. Canada, or
Australia). The Severity Index values for the procedures of blood
harvest are the lowest for sera obtained from donor animals, sera from
non-donor livestock obtained at slaughter (not induced calves), and
single blood harvest of newborns (not induced calves). Note that post
natal vertebrates used for blood harvesting usually come under animal
experimentation legislation.
Vertebrate fetuses used for experiments c.q. procedures
are only subject to relevant protective legislative measures in New
Zealand (the 2nd and 3rd trimester of gestation) the United Kingdom (the
2nd half of gestation), and Australia (not defined). South Africa does
not yet have protective legislative measures for the protection of
animals used for scientific procedures, but a specially designed
guideline has been adopted by many institutes. This code also protects
vertebrate fetuses (not defined). In those countries, FBS harvest by
cardiac puncture or umbilical cord puncture would be considered a
procedure. It may be worth noting that authorities and the serum
industry of those countries which do protect mammal fetuses in their
legislation on the use of animals for scientific procedures, all stated
that the fetus is dead c.q. that the fetal heart is not functioning
anymore at the time of cardiac puncture.
Altogether, the use of livestock sera does not free the
consumer of ethical considerations. The weighing of an in vitro
experiment requiring blood serum might be suggested (e.g. human interest
vs. animal discomfort from bleeding).
For more information on this subject, visit the
following website:
NCA- The Netherlands Centre Alternatives to Animal Use
http://prex.las.vet.uu.nl/nca
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