| Moral reflections on vaccines prepared from cells derived from aborted human foetuses
The human embryo in its preimplantation phase.
Scientific aspects and bioethical considerations
Libreria Editrice Vaticana, Città del Vaticano, 2006 (Other languages: italiano, español, français)
Prospects for Xenotransplantation.
Scientific Aspects and Ethical Considerations
Libreria Editrice Vaticana, Vatican City, 2001 (Other languages: italiano, español, français)
Declaration on the Production and the Scientific and Therapeutic Use of the Human Embryonic Stem Cells
Libreria Editrice Vaticana, Vatican City, 2000 (Other languages: italiano, español, français, deutsch, português)
Reflexions on Cloning
Libreria Editrice Vaticana, Vatican City, 1997 (Other languages: italiano, español, français, deutsch, português)
Other PAV Documents
|5 June, 2005 – Moral reflections on vaccines prepared from cells derived from aborted human foetuses [English, italiano]
|18 April, 2004 – Considerations on the scientific and ethical problems related to vegetative [English, italiano]
| 14 March, 2003 – Proposal for an Ethical Commitment for Researchers in the Field of Biomedicine [English, italiano, español]
PONTIFICIA ACADEMIA PRO VITA
On June 4, 2003, you wrote to His Eminence Cardinal Joseph Ratzinger, with a
copy of this letter forwarded to me, asking to the Sacred Congregation of the Doctrine of
Faith a clarification about the liceity of vaccinating children with vaccines prepared using
cell lines derived from aborted human fetuses. Your question regarded in particular the
right of the parents of these children to oppose such a vaccination when made at school,
mandated by law. As there were no formal guidelines by the magisterium concerning that
topic, you said that catholic parents were often challenged by State Courts, Health Officials
and School Administrators when they filled religious exemptions for their children to this
type of vaccination.
This Pontifical Academy for Life, carrying out the commission entrusted to us by
the Congregation for the Doctrine of Faith, in answer to your request, has proceeded to a
careful examination of the question of these "tainted" vaccines, and has produced as a
result a study (in Italian) that has been realized with the help of a group of experts. This
study has been approved as such by the Congregation and we send you, there enclosed, an
English translation of a synthesis of this study. This synthesis can be brought to the
knowledge of the interested officials and organisms.
A documented paper on the topic will be published in the journal "Medicina e
Morale", edited by the Centra di Bioetica della Universita Cattolica in Rome.
The study, its synthesis, and the translation of this material took some time. We
apologize for the delay.
With my best regards,
00193 Roma – Via della Conciliazione, 1 – Tel. 06 698.82423 – 06 698.81693 – Fax 06 698.82014
E-mail: email@example.com — Sito web: www.academiavita.org
from Il Presidente
Mrs Debra L.Vinnedge Vatican City, June 9 2005
Executive Director, Children of God for Life
943 Deville Drive East
Dear Mrs Debra L.Vinnedge,
ON VACCINES PREPARED FROM
DERIVED FROM ABORTED HUMAN FOETUSES
The matter in question regards the lawfulness of production, distribution and
use of certain vaccines whose production is connected with acts of procured abortion.
It concerns vaccines containing live viruses which have been prepared from human cell
lines of foetal origin, using tissues from aborted human foetuses as a source of such
cells. The best known, and perhaps the most important due to its vast distribution
and its use on an almost universal level, is the vaccine against Rubella (German
Rubella and its vaccine
Rubella (German measles)1 is a viral illness caused by a Togavirus of the genus
Rubivirus and is characterized by a maculopapular rash. It consists of an infection
which is common in infancy and has no clinical manifestations in one case out of two,
is self-limiting and usually benign. Nonetheless, the German measles virus is one of
the most pathological infective agents for the embryo and foetus. When a woman
catches the infection during pregnancy, especially during the first trimester, the risk of
foetal infection is very high (approximately 95%). The virus replicates itself in the
placenta and infects the foetus, causing the constellation of abnormalities denoted by
the name of Congenital Rubella Syndrome. For example, the severe epidemic of
German measles which affected a huge part of the United States in 1964 thus caused
20,000 cases of congenital rubella2, resulting in 11,250 abortions (spontaneous or
surgical), 2,100 neonatal deaths, 11,600 cases of deafness, 3,580 cases of blindness,
1,800 cases of mental retardation. It was this epidemic that pushed for the
development and introduction on the market of an effective vaccine against rubella,
thus permitting an effective prophylaxis against this infection.
The severity of congenital rubella and the handicaps which it causes justify
systematic vaccination against such a sickness. It is very difficult, perhaps even
impossible, to avoid the infection of a pregnant woman, even if the rubella infection
of a person in contact with this woman is diagnosed from the first day of the eruption
of the rash. Therefore, one tries to prevent transmission by suppressing the reservoir
of infection among children who have not been vaccinated, by means of early
immunization of all children (universal vaccination). Universal vaccination has
resulted in a considerable fall in the incidence of congenital rubella, with a general
incidence reduced to less than 5 cases per 100,000 livebirths. Nevertheless, this
progress remains fragile. In the United States, for example, after an overwhelming
reduction in the number of cases of congenital rubella to only a few cases annually,
1 J. E. Banatvala, D.W.G. Brown, Rubella, The Lancet, 3rd April 2004, vol. 363, No. 9415, pp.1127-
2 Rubella , Morbidity and Mortality Weekly Report, 1964, vol. 13, p.93. S.A. Plotkin, Virologic
Assistance in the Management of German Measles in Pregnancy, JAMA, 26th October 1964, vol.190,
i.e. less than 0.1 per 100,000 live births, a new epidemic wave came on in 1991, with
an incidence that rose to 0.8/100,000. Such waves of resurgence of German measles
were also seen in 1997 and in the year 2000. These periodic episodes of resurgence
make it evident that there is a persistent circulation of the virus among young adults,
which is the consequence of insufficient vaccination coverage. The latter situation
allows a significant proportion of vulnerable subjects to persist, who are a source of
periodic epidemics which put women in the fertile age group who have not been
immunized at risk. Therefore, the reduction to the point of eliminating congenital
rubella is considered a priority in public health care.
Vaccines currently produced using human cell lines that come from aborted foetuses
To date, there are two human diploid cell lines which were originally prepared from
tissues of aborted foetuses ( in 1964 and 1970) and are used for the preparation of
vaccines based on live attenuated virus: the first one is the WI-38 line (Winstar
Institute 38), with human diploid lung fibroblasts, coming from a female foetus that
was aborted because the family felt they had too many children (G. Sven et al., 1969).
It was prepared and developed by Leonard Hayflick in 1964 (L. Hayflick, 1965; G.
Sven et al., 1969)3 and bears the ATCC number CCL-75. WI-38 has been used for the
preparation of the historical vaccine RA 27/3 against rubella (S.A. Plotkin et al,
1965)4. The second human cell line is MRC-5 (Medical Research Council 5) (human,
lung, embryonic) (ATCC number CCL-171), with human lung fibroblasts coming
from a 14 week male foetus aborted for "psychiatric reasons" from a 27 year old
woman in the UK. MRC-5 was prepared and developed by J.P. Jacobs in 1966 (J.P.
Jacobs et al, 1970)5. Other human cell lines have been developed for pharmaceutical
needs, but are not involved in the vaccines actually available6.
3. L. Hayflick, The Limited In Vitro Lifetime of Human Diploid Cell Strains, Experimental Cell
Research, March 1965, vol.37, no. 3, pp. 614-636.
G. Sven, S. Plotkin, K. McCarthy, Gamma Globulin Prophylaxis; Inactivated Rubella Virus;
Production and Biological Control of Live Attenuated Rubella Virus Vaccines, American journal of
Diseases of Children, August 1969, vol. 118, no. 2, pp.372-381.
4.S. A. Plotkin, D. Cornfeld, Th.H. Ingalls, Studies of Immunization With Living Rubella Virus, Trials in
Children With a Strain coming from an Aborted Fetus, American Journal of Diseases in children,
October 1965, vol. 110, no. 4, pp.381-389.
5 J.P. Jacobs, C.M. Jones, J.P. Bailie, Characteristics of a Human Diploid Cell Designated MRC-5,
Nature, 11th July 1970, vol.277, pp.168-170.
6 Two other human cell lines, that are permanent, HEK 293 aborted fetal cell line, from primary human
embryonic kidney cells transformed by sheared adenovirus type 5 (the fetal kidney material was
obtained from an aborted fetus, in 1972 probably), and PER.C6, a fetal cell line created using retinal
tissue from an 18 week gestation aborted baby, have been developed for the pharmaceutical
manufacturing of adenovirus vectors (for gene therapy). They have not been involved in the making of
any of the attenuated live viruses vaccines presently in use because of their capacity to develop
tumorigenic cells in the recipient. However some vaccines, still at the developmental stage, against
Ebola virus (Crucell,NV and the Vaccine Research Center of the National Institutes of Health's Allergy
and Infectious Diseases, NIAID), HIV (Merck), influenza (Medlmmune, Sanofi pasteur), Japanese
encephalitis (Crucell N.V. and Rhein Biotech N.V.) are prepared using PER.C6® cell line (Crucell
N.V., Leiden, The Netherlands).
The vaccines that are incriminated today as using human cell lines from aborted
foetuses, WI-38 and MRC-5, are the following:7
A) Live vaccines against rubella8 :
– the monovalent vaccines against rubella Meruvax®!! (Merck) (U.S.), Rudivax®
(Sanofi Pasteur, Fr.), and Ervevax® (RA 27/3) (GlaxoSmithKline, Belgium);
– the combined vaccine MR against rubella and measles, commercialized with the
name of M-R-VAX® (Merck, US) and Rudi-Rouvax® (AVP, France);
– the combined vaccine against rubella and mumps marketed under the name of
Biavax®!! (Merck, U.S.),
– the combined vaccine MMR (measles, mumps, rubella) against rubella, mumps and
measles, marketed under the name of M-M-R® II (Merck, US), R.O.R.®,
Trimovax® (Sanofi Pasteur, Fr.), and Priorix® (GlaxoSmithKline UK).
B) Other vaccines, also prepared using human cell lines from aborted foetuses:
– two vaccines against hepatitis A, one produced by Merck (VAQTA), the other one
produced by GlaxoSmithKline (HAVRIX), both of them being prepared using MRC-
– one vaccine against chicken pox, Varivax®, produced by Merck using WI-38 and
– one vaccine against poliomyelitis, the inactivated polio virus vaccine Poliovax®
(Aventis-Pasteur, Fr.) using MRC-5;
– one vaccine against rabies, Imovax®, produced by Aventis Pasteur, harvested from
infected human diploid cells, MRC-5 strain;
– one vaccine against smallpox, AC AM 1000, prepared by Acambis using MRC-5,
still on trial.
The position of the ethical problem related to these vaccines
7 Against these various infectious diseases, there are some alternative vaccines that are prepared using
animals' cells or tissues, and are therefore ethically acceptable. Their availability depends on the country
in question. Concerning the particular case of the United States, there are no options for the time being
in that country for the vaccination against rubella, chickenpox and hepatitis A, other than the vaccines
proposed by Merck, prepared using the human cell lines WI-38 and MRC-5. There is a vaccine against
smallpox prepared with the Vero cell line (derived from the kidney of an African green monkey),
ACAM2000 (Acambis-Baxter) ( a second-generation smallpox vaccine, stockpiled, not approved in the
US), which offers, therefore, an alternative to the Acambis 1000. There are alternative vaccines against
mumps (Mumpsvax, Merck, measles (Attenuvax, Merck), rabies (RabAvert, Chiron therapeutics),
prepared from chicken embryos. (However serious allergies have occurred with such vaccines),
poliomyelitis (IPOL, Aventis-Pasteur, prepared with monkey kidney cells) and smallpox (a thirdgeneration
smallpox vaccine MVA, Modified Vaccinia Ankara, Acambis-Baxter).
In Europe and in Japan, there are other vaccines available against rubella and hepatitis A, produced
using non-human cell lines. The Kitasato Institute produce four vaccines against rubella, called
Takahashi, TO-336 and Matuba, prepared with cells from rabbit kidney, and one (Matuura) prepared
with cells from a quail embryo. The Chemo-sero-therapeutic Research Institute Kaketsuken produce
one another vaccine against hepatitis A, called Ainmugen, prepared with cells from monkey kidney.
The only remaining problem is with the vaccine Varivax® against chicken pox, for which there is no
8 The vaccine against rubella using the strain Wistar RA27/3 of live attenuated rubella virus, adapted
and propagated in WI-38 human diploid lung fibroblasts is at the centre of present controversy
regarding the morality of the use of vaccines prepared with the help of human cell lines coming from
From the point of view of prevention of viral diseases such as German
measles, mumps, measles, chicken pox and hepatitis A, it is clear that the making of
effective vaccines against diseases such as these, as well as their use in the fight
against these infections, up to the point of eradication, by means of an obligatory
vaccination of all the population at risk, undoubtedly represents a "milestone" in the
secular fight of man against infective and contagious diseases.
However, as the same vaccines are prepared from viruses taken from the
tissues of foetuses that had been infected and voluntarily aborted, and the viruses were
subsequently attenuated and cultivated from human cell lines which come likewise
from procured abortions, they do not cease to pose ethical problems. The need to
articulate a moral reflection on the matter in question arises mainly from the
connection which exists between the vaccines mentioned above and the procured
abortions from which biological material necessary for their preparation was obtained.
If someone rejects every form of voluntary abortion of human foetuses, would
such a person not contradict himself/herself by allowing the use of these vaccines of
live attenuated viruses on their children? Would it not be a matter of true (and illicit)
cooperation in evil, even though this evil was carried out forty years ago?
Before proceeding to consider this specific case, we need to recall briefly the
principles assumed in classical moral doctrine with regard to the problem of
cooperation in evil 9, a problem which arises every time that a moral agent perceives
the existence of a link between his own acts and a morally evil action carried out by
The principle of licit cooperation in evil
The first fundamental distinction to be made is that between formal and
material cooperation. Formal cooperation is carried out when the moral agent
cooperates with the immoral action of another person, sharing in the latter's evil
intention. On the other hand, when a moral agent cooperates with the immoral action
of another person, without sharing his/her evil intention, it is a case of material
Material cooperation can be further divided into categories of immediate
(direct) and mediate (indirect), depending on whether the cooperation is in the
execution of the sinful action per se, or whether the agent acts by fulfilling the
conditions – either by providing instruments or products – which make it possible to
commit the immoral act. Furthermore, forms of proximate cooperation and remote
cooperation can be distinguished, in relation to the "distance" (be it in terms of
temporal space or material connection) between the act of cooperation and the sinful
act committed by someone else. Immediate material cooperation is always proximate,
while mediate material cooperation can be either proximate or remote.
Formal cooperation is always morally illicit because it represents a form of
direct and intentional participation in the sinful action of another person.10 Material
9 D.M. Prummer O. Pr., De cooperatione ad malum, in Manuale Theologiae Moralis secundum
Principia S. Thomae Aquinatis, Tomus I, Friburgi Brisgoviae, Herder & Co., 1923, Pars I, Trat. IX,
Caput III, no. 2, pp. 429-434.
.K.H. Peschke, Cooperation in the sins of others, in Christian Ethics. Moral Theology in the Light of
Vatican II, vol.1, General Moral Theology, C. Goodliffe Neale Ltd., Arden Forest Industrial Estate,
Alcester, Warwickshire, B49 6Er, revised edition, 1986, pp. 320-324.
10 A. Fisher, Cooperation in Evil, Catholic Medical Quarterly, 1994, pp. 15-22.
cooperation can sometimes be illicit (depending on the conditions of the "double
effect" or "indirect voluntary" action), but when immediate material cooperation
concerns grave attacks on human life, it is always to be considered illicit, given the
precious nature of the value in question11.
A further distinction made in classical morality is that between active (or
positive) cooperation in evil and passive (or negative) cooperation in evil, the former
referring to the performance of an act of cooperation in a sinful action that is carried
out by another person, while the latter refers to the omission of an act of denunciation
or impediment of a sinful action carried out by another person, insomuch as there was
a moral duty to do that which was omitted 12. Passive cooperation can also be formal
or material, immediate or mediate, proximate or remote. Obviously, every type of
formal passive cooperation is to be considered illicit, but even passive material
cooperation should generally be avoided, although it is admitted (by many authors)
that there is not a rigorous obligation to avoid it in a case in which it would be greatly
difficult to do so.
Application to the use of vaccines prepared from cells coming from embryos or
foetuses aborted voluntarily
In the specific case under examination, there are three categories of people
who are involved in the cooperation in evil, evil which is obviously represented by the
action of a voluntary abortion performed by others: a) those who prepare the vaccines
using human cell lines coming from voluntary abortions; b) those who participate in
the mass marketing of such vaccines; c) those who need to use them for health
Firstly, one must consider morally illicit every form of formal cooperation
(sharing the evil intention) in the action of those who have performed a voluntary
abortion, which in turn has allowed the retrieval of foetal tissues, required for the
preparation of vaccines. Therefore, whoever – regardless of the category to which he
belongs — cooperates in some way, sharing its intention, to the performance of a
voluntary abortion with the aim of producing the above-mentioned vaccines,
participates, in actuality, in the same moral evil as the person who has performed that
abortion. Such participation would also take place in the case where someone, sharing
the intention of the abortion, refrains from denouncing or criticizing this illicit action,
although having the moral duty to do so (passive formal cooperation).
.D. Tettamanzi, Cooperazione, in Dizionario di Bioetica, S. Leone, S. Privitera ed., Istituto Siciliano di
Bioetica, EDB-ISB, 1994, pp.194-198.
.L. Melina, La cooperazione con azioni moralmente cattive contra la vita umana, in Commentario
Interdisciplinare alia "Evangelium Vitae", E. Sgreccia, Ramon Luca Lucas ed., Libreria Editrice
Vaticana, 1997, pp.467-490.
.E. Sgreccia, Manuale di Bioetica, vol. I, Reprint of the third edition, Vita e Pensiero, Milan, 1999,
11 Cf. John Paul II, Enc. Evangelium Vitae, no. 74.
12 No. 1868 of the Catechism of the Catholic Church.
In a case where there is no such formal sharing of the immoral intention of the
person who has performed the abortion, any form of cooperation would be material,
with the following specifications.
As regards the preparation, distribution and marketing of vaccines produced as
a result of the use of biological material whose origin is connected with cells coming
from foetuses voluntarily aborted, such a process is stated, as a matter of principle,
morally illicit, because it could contribute in encouraging the performance of other
voluntary abortions, with the purpose of the production of such vaccines.
Nevertheless, it should be recognized that, within the chain of production-distributionmarketing,
the various cooperating agents can have different moral responsibilities.
However, there is another aspect to be considered, and that is the form of
passive material cooperation which would be carried out by the producers of these
vaccines, if they do not denounce and reject publicly the original immoral act (the
voluntary abortion), and if they do not dedicate themselves together to research and
promote alternative ways, exempt from moral evil, for the production of vaccines for
the same infections. Such passive material cooperation, if it should occur, is equally
As regards those who need to use such vaccines for reasons of health, it must
be emphasized that, apart from every form of formal cooperation, in general, doctors
or parents who resort to the use of these vaccines for their children, in spite of
knowing their origin (voluntary abortion), carry out a form of very remote mediate
material cooperation, and thus very mild, in the performance of the original act of
abortion, and a mediate material cooperation, with regard to the marketing of cells
coming from abortions, and immediate, with regard to the marketing of vaccines
produced with such cells. The cooperation is therefore more intense on the part of the
authorities and national health systems that accept the use of the vaccines.
However, in this situation, the aspect of passive cooperation is that which
stands out most. It is up to the faithful and citizens of upright conscience (fathers of
families, doctors, etc.) to oppose, even by making an objection of conscience, the ever
more widespread attacks against life and the "culture of death" which underlies them.
From this point of view, the use of vaccines whose production is connected with
procured abortion constitutes at least a mediate remote passive material cooperation to
the abortion, and an immediate passive material cooperation with regard to their
marketing. Furthermore, on a cultural level, the use of such vaccines contributes in the
creation of a generalized social consensus to the operation of the pharmaceutical
industries which produce them in an immoral way.
Therefore, doctors and fathers of families have a duty to take recourse to
alternative vaccines13 (if they exist), putting pressure on the political authorities and
l3 The alternative vaccines in question are those that are prepared by means of cell lines which are not
of human origin, for example, the Vero cell line (from monkeys) (D. Vinnedge), the kidney cells of
rabbits or monkeys, or the cells of chicken embryos. However, it should be noted that grave forms of
allergy have occurred with some of the vaccines prepared in this way. The use of recombinant DNA
technology could lead to the development of new vaccines in the near future which will no longer
require the use of cultures of human diploid cells for the attenuation of the virus and its growth, for
such vaccines will not be prepared from a basis of attenuated virus, but from the genome of the virus
and from the antigens thus developed (G. C. Woodrow, W.M. McDonnell and F.K. Askari). Some
experimental studies have already been done using vaccines developed from DNA that has been
derived from the genome of the German measles virus. Moreover, some Asiatic researchers are trying to
use the Varicella virus as a vector for the insertion of genes which codify the viral antigens of
health systems so that other vaccines without moral problems become available. They
should take recourse, if necessary, to the use of conscientious objection 14 with regard
to the use of vaccines produced by means of cell lines of aborted human foetal origin.
Equally, they should oppose by all means (in writing, through the various
associations, mass media, etc.) the vaccines which do not yet have morally acceptable
alternatives, creating pressure so that alternative vaccines are prepared, which are not
connected with the abortion of a human foetus, and requesting rigorous legal control
of the pharmaceutical industry producers.
As regards the diseases against which there are no alternative vaccines which
are available and ethically acceptable, it is right to abstain from using these vaccines
if it can be done without causing children, and indirectly the population as a whole, to
undergo significant risks to their health. However, if the latter are exposed to
considerable dangers to their health, vaccines with moral problems pertaining to them
may also be used on a temporary basis. The moral reason is that the duty to avoid
passive material cooperation is not obligatory if there is grave inconvenience.
Moreover, we find, in such a case, a proportional reason, in order to accept the use of
these vaccines in the presence of the danger of favouring the spread of the
pathological agent, due to the lack of vaccination of children. This is particularly true
in the case of vaccination against German measles15.
In any case, there remains a moral duty to continue to fight and to employ
every lawful means in order to make life difficult for the pharmaceutical industries
which act unscrupulously and unethically. However, the burden of this important
battle cannot and must not fall on innocent children and on the health situation of the
population – especially with regard to pregnant women.
To summarize, it must be confirmed that:
-there is a grave responsibility to use alternative vaccines and to make a conscientious
objection with regard to those which have moral problems;
– as regards the vaccines without an alternative, the need to contest so that others may
be prepared must be reaffirmed, as should be the lawfulness of using the former in the
meantime insomuch as is necessary in order to avoid a serious risk not only for one's
Rubella. These studies are still at a preliminary phase and the refinement of vaccine preparations which
can be used in clinical practice will require a lengthy period of time and will be at high costs. .D.
Vinnedge, The Smallpox Vaccine, The National Catholic Bioethics Quarterly, Spring 2000, vol.2, no. 1,
p. 12. .G.C. Woodrow, An Overview of Biotechnology As Applied to Vaccine Development, in «New
Generation Vaccines)), G.C. Woodrow, M.M. Levine eds., Marcel Dekker Inc., New York and Basel,
1990, see pp.32-37. W.M. McDonnell, F.K. Askari, Immunization, JAMA, 10th December 1997,
vol.278, no.22, pp.2000-2007, see pp. 2005-2006.
14 Such a duty may lead, as a consequence, to taking recourse to "objection of conscience" when the
action recognized as illicit is an act permitted or even encouraged by the laws of the country and poses a
threat to human life. The Encyclical Letter Evangelium Vitae underlined this "obligation to oppose" the
laws which permit abortion or euthanasia "by conscientious objection" (no.73)
15 This is particularly true in the case of vaccination against German measles, because of the danger of
Congenital Rubella Syndrome. This could occur, causing grave congenital malformations in the foetus,
when a pregnant woman enters into contact, even if it is brief, with children who have not been
immunized and are carriers of the virus. In this case, the parents who did not accept the vaccination of
their own children become responsible for the malformations in question, and for the subsequent
abortion of foetuses, when they have been discovered to be malformed.
own children but also, and perhaps more specifically, for the health conditions of the
population as a whole – especially for pregnant women;
– the lawfulness of the use of these vaccines should not be misinterpreted as a
declaration of the lawfulness of their production, marketing and use, but is to be
understood as being a passive material cooperation and, in its mildest and remotest
sense, also active, morally justified as an extrema ratio due to the necessity to provide
for the good of one's children and of the people who come in contact with the
children (pregnant women);
– such cooperation occurs in a context of moral coercion of the conscience of parents,
who are forced to choose to act against their conscience or otherwise, to put the health
of their children and of the population as a whole at risk. This is an unjust alternative
choice, which must be eliminated as soon as possible.