Lessons from anti-thalassemia campaigns in Italy, before prenatal
diagnosis
Medicina nei secoli, 2003, 15, 1
Stefano Canali
Gilberto Corbellini
Sezione di storia della medicina
Dipartimento di medicina molecolare e patologia
Università degli studi di Roma “La Sapienza”
Summary: The essay reconstructs the campaign against thalassemia carried out by means of
population screening and pre-marriage counselling for about twenty years in Italy, immediately
after the relationship between microcythemia, Cooley's anemia and the genetic bases of the disorder
had been established. We examine the Italian contributions to the understanding of the genetics and
clinical treatment of thalassemic disorders, and analyze the approaches to prevention as well as the
results obtained by the first campaign against a genetic disease, conceived and largely implemented
by Ezio Silvestroni and Ida Bianco. We will discuss the resistances encountered by the campaign
owing to the cultural and organizational backwardness of the medical community and the public
health service in Italy, as well as the explanations and interpretations of the problematic results of
these experiments in terms of the reduction of morbidity. It will be pointed out that the objective of
genetic counselling in those programmes insisted on the concept of prevention of the disease at the
population level rather than according to the idea, which emerged only in the 'seventies in the field
of genetic medicine, of merely providing elements of information of use in making an individual
informed choice
Keywords: History of Thalassemia, History of Genetic screening, Pre-marriage counselling, Ezio
Silvestroni, Ida Bianco
Running title: Lessons from antithalassemia campaigns in Italy
1
Introduction
The beta-thalassemia prevention action undertaken by the health services in the early 'seventies
in various countries by means of the genetic screening of the population and prenatal diagnosis,
made it possible, on the basis of pre- or post-nuptial reproductive decisions - in particular by the
selective abortion of homozygous foetuses - to prevent almost entirely the birth of children
suffering from the effects of thalassemia. Several of these national and regional experiments have
been analysed and, as far as Italy is concerned, particular emphasis has been laid on the campaign
carried out in Sardinia1. A number of different socio-ethical problems were reported, associated
with the anti-thalassemia campaign, above all in national contexts in which beta-thalassemia
involved ethnic minorities, but also in operations at the level of the general population, such as the
one carried out at Cyprus2.
Before the prevention of beta-thalassemia was in a position to exploit the new prenatal diagnosis
techniques, the campaign against this disease had been attempted by means of screening and premarriage counselling for about twenty years in Italy, immediately after the relationship between
microcythemia and Cooley's anemia and the genetic bases of the disorder had been established.
The present article reconstructs this experiment, schematically examining the Italian
contributions to the understanding of the genetics and clinical treatment of thalassemic disorders,
and analysing the lines of approach to prevention as well as the results obtained. An examination
will be made of the premises and methods underlying what was the first campaign against a genetic
disease, conceived and largely implemented by Ezio Silvestroni and Ida Bianco. Furthermore, a
discussion will be presented of the resistance encountered by the campaign owing to the cultural
and organizational backwardness of the medical community and the public health service in Italy
and the official stance adopted by the Roman Catholic Church. Lastly, an analysis will be presented
of the explanations and interpretations of the problematic results of these experiments in terms of
the reduction of morbidity, showing that the objective of genetic counselling in those programmes
insisted on the concept of prevention of the disease at the population level rather than according to
the idea, which emerged only in the 'seventies in the field of genetic medicine, of merely providing
elements of information of use in making an individual informed choice3.
Silvestroni and Bianco's experience became a reference model for the thalassemia prevention
programmes carried out in the 'seventies in Greece and Cyprus, and even though it was hastily
judged to be superseded by the advent of prenatal diagnosis, it contains important lessons of still
topical interest. In particular, several experiments in health care education carried out within the
programme of the campaign against thalassemia in Italy can be taken as models in addressing the
current need to promote cultural awareness concerning genetic testing in medicine4.
2
Phases and controversies in the Italian contribution to the discovery of the
genetics of thalassemia
The fact that the first thalassemia prevention programme was run in Italy was the consequence
of the intense studies carried out on this disease by a number of Italian researchers, who made a
significant contribution to introducing some form of order into the relationship between clinical
signs and the genetic basis of thalassemia.
In 1932, when George Whipple introduced the term “thalassemia”5, Thomas Cooley noticed that
the disease had an evident familial incidence6. Later, Heinrich Lehndorf assumed that Cooley’s
anemia was an inherited disease originally due to a genetic mutation7.
In the same period Ferdinando Micheli and collaborators (1935), Angelini (1937), Jean
Caminopetros (1937) observed distinctive, even if minimal, hematological traits in healthy parents8.
Then Maxwell Wintrobe and William Dameshek recognized the relationship between these
hematological abnormalities and minor forms of thalassemia9. Meanwhile Jean Caminopetros
(1937) postulated that clinically healthy people could transmit the disease as a recessive Mendelian
trait10.
Alan Moncrieff and Lionel Ernest Whitby had already suggested the involvement of a
Mendelian mechanism in 193411. Ignazio Gatto proposed in 1941-42 that thalassemia was a
hereditary condition, lethal in the homozygote (“omozigote-malattia”) and representing in the
heterozygote only a minor and non pathological trait (“eterozigote-stigmata”)12.
In 1943, Ezio Silvestroni and Ida Bianco described an inborn and hereditary hematological
anomaly in healthy people that they subsequently called microcythemia13. At the same time,
Silvestroni and Bianco established the genetical relationship between thalassemia and
microcythemia by studying several people with Cooley’s anemia14. At the end of these
investigations, Silvestroni and Bianco showed conclusively that microcythemia was a Mendelian
character, and its homozygotic condition corresponded to Cooley’s disease15. These results tallied
with the evidence obtained from independent studies conducted in USA by Dameshek16, and
especially by William Valentine and James Neel at University of Rochester17.
Silvestroni and Bianco's results were greeted unenthusiastically and even vigorously challenged
by the Italian scientific community. A bitter controversy arose over the nature and priority of the
discovery of microcythemia, as well as over the demonstration of the relationship between this
condition and Cooley's anemia. Several Italian physicians had for various reasons had the occasion
to study microcythemic individuals, and had reported forms of familiarity in the hematological
features of the types of thalassemia; they also described, without understanding it, the link between
Cooley's anemia, Rietti-Greppi-Micheli's disease and the microcythemic condition18. Silvestroni
and Bianco, who were still only young assistant physicians at the time and enjoyed no effective
academic protection, were isolated inside the medical community. Indeed, in the pure feudal style
prevailing in the Italian universities in the 'fifties, Ezio Silvestroni was systematically failed his
competitive examinations for the award of a chair, and soon had to abandon all hope of academic
success. Both members of the couple were then pushed out of the university in 1957 as the result of
a change of management of the Clinical Medicine Institute where they worked as assistants19. Partly
for this reason, and partly due to the envy and opposition they encountered, their proposals on
prevention received a very cool reception from those responsible for Italian health care policy.
3
From epidemiological investigations to the prevention model
Between 1943, the year in which they began their research on microcythemia and 1948,
Silvestroni and Bianco carried out extensive epidemiological studies throughout Italy and were the
first in the case of thalassemia to draw up an accurate map of the distribution of the disease in
Italy20. Their research results pointed to an alarming situation, characterized by the presence of
numerous microcythemic foci scattered over the country, in particular in the Po valley area and the
islands, i.e. Sardinia and Sicily, where the incidence of carriers sometimes exceeded 20% of the
population.
For about twenty years, until the mid ’60s, the extensive root and branch epidemiological study
carried out by Silvestroni and Bianco in the whole of Italy, involving about 100,000 subjects, was
based on using a rapid method they themselves had devised to diagnose microcythemia21.
Starting from an understanding of the genetic relationship between microcythemia and
thalassemia, Silvestroni and Bianco suggested that it was possible to implement prevention by
avoiding marriage and procreation between microcythemics. In the session of the Accademia
Medica di Roma held on 30 November 1946, the two researchers announced the results of their
C.N.R. funded research on the frequency of microcythemia in the Ferrara area and in the
neighbouring regions (2,393 subjects examined). The results confirmed the link between
microcythemia and Cooley's anemia. According to Silvestroni and Bianco they also demonstrated
the possibility of using suitable prophylactic measures for the purpose of preventing (that is, by preventing
marriages between microcythemia carriers) the onset of this form of the disease22.
Silvestroni reaffirmed this idea in 1949, at the 50th Congress of the Società Italiana di Medicina
Interna, pointing out that
also in America there is growing awareness that our present understanding of the hereditary nature of Cooley's
anemia means that eugenic counselling can be given to young couples in whom one or both partners are microcythemia
carriers23.
In the course of the same Congress other speakers described possible strategies for the
prevention of thalassemia, also in the wake of the eugenic ideas popular at the time. Giovanni Di
Guglielmo proposed the sterilization of microcythemics while, when participating in the discussion,
the anthropologist Sergio Sergi, a leading figure in the eugenic debate in Italy, suggested
performing a compulsory blood test on the entire school population, which had also already been
suggested by Silvestroni and Bianco.
3.1
Silvestroni and Bianco's prevention model: general principles
Formulated in the early ’50s, Silvestroni and Bianco's prevention model was based essentially
on the identification of carriers by means of mass screenings and on pre-marriage prevention. At the
time, this was the only possible course of action after the link between microcythemia and Cooley's
anemia had been demonstrated, and was set up and implemented some two decades before the
advent of prenatal diagnosis24.
The search for microcythemia", wrote the two Roman researchers, "has an obvious importance, not only for the
purpose of identifying Cooley's anemia in patients that are already sick and anemic […] the presence, always clearly
identifiable in parents suffering from Cooley's anemia, of the complex of hematological characters representing
microcythemia, affords early recognition of all those families that, in their turn, may give birth to children suffering
from Cooley's anemia, and is a precious element in ensuring an adequate and feasible prophylaxis of this disease. It thus
became possible in those regions, such as the Ferrara area, characterized by a high incidence of Cooley's anemia, by
identifying microcythemia carriers through the special blood test centres, to avoid marriages between microcythemia
carriers, which would be sufficient (except in rather rare and hard to interpret cases of families in which the disease is
declared when only one parent is a carrier of the anomaly) to avoid the onset of new cases of Cooley's anemia25.
Silvestroni and Bianco on several occasions called for the microcythemia test to be made
compulsory for couples planning to get married.
3.1.1 The importance of health care education and information
From the outset the two researchers grasped the importance for the purpose of prevention of
information and health care and "eugenic" education. In the long report he delivered to the 50th
Congress of the Società Italiana di Medicina Interna held in Rome, Silvestroni appealed to the state
for help in carrying out a sweeping national awareness campaign on the problem, a campaign of
education able to set in motion the formation of a eugenic sensitivity, that is, aimed at reducing the
number of marriage between carriers, the only instrument available at the time to prevent Cooley's
anemia26.
Silvestroni's ideas and proposed prophylaxis aroused a strong echo in the media (see, among
others, La Settimana Incom, 3 November 1949, L’Elefante, 5 November 1949)27.
In order to disseminate knowledge about thalassemia and methods of prophylaxis, Silvestroni
and Bianco in 1951 made a documentary film, which they immediately set about screening for
physicians, health care professionals and the general public.
4
1954-1971: prevention of thalassemia in the framework of the radical
changes in health care policy in Italy
Only towards the mid ’50s did the Italian health authorities begin to take an interest in the
problem of thalassemia. In that period Silvestroni and Bianco finally succeeded in getting the
political will of the academic world to converge with that of the health care authorities. Sufficient
funds were now forthcoming from different sources to be able to undertake a programme of
prevention, which was actually the first in the world for thalassemia.
4.1
The birth of the Rome Microcythemia Centre
Amid numerous difficulties, Silvestroni succeeded in raising the level of awareness of the Alto
Commissariato per l’Igiene e la Sanità Pubblica – ACIS28, a body that had already, on various
occasions, made available small financial contributions for the research and population studies
carried out together with Ida Bianco. As immediate objective he proposed to set up a centre for the
campaign against microcythemia.
Silvestroni at the time was assistant lecturer in general clinical practice and medical therapy at
the University of Rome. His academic position was therefore comparatively weak for the purpose
of carry out a project that was quite burdensome and presented complex organizational obstacles.
Premises and funding were needed to set up the centre, purchase equipment and get the centre
operational. Instrumental in this connection was the help offered by Vittorio Puntoni, then Head of
the Faculty of Medicine and Director of the Institute of Hygiene. Puntoni had realized the
importance of the work being done by Silvestroni and Bianco as well as the social significance of a
research centre for microcythemia and the prevention of Cooley's anemia. He had invited the two
researchers to write a long article, published in 1953 in Annali di Sanità pubblica, which
summarized their research results and pointed to the need to carry out effective prevention measures
through the direct action of the national health care authorities29.
In 1954 Puntoni had the centre set up inside his institute, in premises that had been freed by the
transfer of the museum and the library of the history of medicine, and sponsored Silvestroni's
request to ACIS in a formal letter sent on 25 July 1954 to the ACIS Alto Commissario, Tiziano
Tessitori30.
On the following 18 September, Tessitori informed Puntoni that a grant of 4,450,000 Lire (the
equivalent to about 155,800 Euro in January 2002 values) had been offered for the creation of a
microcythemia study centre directed by Ezio Silvestroni31. In his letter Tessitori expressed the hope
that
the problem of microcythemia, of the social importance of which this High Commissariat is fully aware, may be
thoroughly studied and determined, above all with regard to Cooley's anemia32.
ACIS' primary objective was thus prevention and the Centre was actually the beginning of the
first Italian, and indeed world, campaign of thalassemia prophylaxis. The mandate received by the
Centre was however more comprehensive, and ranged from clinical practice to experimental
research, thus basically covering the same ground as Silvestroni had already travelled over with Ida
Bianco:
1)
organization of the health care services for the care and treatment of those suffering from
Cooley's anemia and other microcythemic anemias in all the Italian regions badly
affected by these diseases;
2)
extension of epidemiological research, in order to determine more precisely the extension
and extent of the microcythemic phenomenon in Italy as a whole;
3)
research and application of the more effective means of treatment against Cooley's
anemia and the microcythemic anemias;
4)
implementation of pre-marriage prophylaxis against Cooley's anemia;
5)
performance of studies and research in the field of microcythemia.
Also the Rockfeller Foundation recognized the importance of Silvestroni and Bianco's research
and results and in 1954, by means of a genetics research programme coordinated by Giuseppe
Montalenti, it decided to financially support the two physicians and the newly created Centre in
order to ensure greater development of
the eugenic aspect of the microcythemic problem, the establishment of official registers of persons carrying this
gene, and marriage counseling in some form33.
However, the Italian geneticist did not take up the suggestion and allocated most of the available
funds to research on population genetics.
In 1955 the Centre opened a free day hospital service for the vetting and care of thalassemia
patients. Subsequently, in 1956, work began on networking the peripheral centres in the Italian
regions with the highest incidence of thalassemia. With the help of a new financial contribution,
first from ACIS and then from the newly established Ministry of Health (instituted by Law 13
March 1958, no. 296), between 1956 and 1961 seven microcythemia centres or sections, as they
were called, were set up and carried on their activities in close collaboration with the Rome
Centre34.
4.2
1961: Thalassemia as a social disease and the birth of the Associazione Nazionale per la
Lotta contro la Microcitemia in Italia - ANLMI
On 5 December 1961, the Consiglio Superiore di Sanità, when finalizing the last hearings
regarding the determination of social diseases for the purposes of applying the Decreto del
Presidente della Repubblica 11 February 1961, Chapter II of which provided for the institution of
“special social disease centres for the protection of the health of the population”, convened
Silvestroni on the subject of microcythemia and Cooley's anemia.
In his report Silvestroni pointed out the need for state intervention owing to the epidemiological
dimension of thalassemia, the high cost of treatment for the patients, unaffordable by the majority
of Italian families, but above all in order to achieve large-scale implementation
as a means of immediate and certain effectiveness, of pre-marriage prophylaxis against this disease35.
The onset of Cooley's anemia – Silvestroni went on –is determined by the homozygous condition of the
microcythemia and it is thus possible to avoid it by preventing marriage between microcythemics and recommending
marriage between microcythemics and normal subjects. This led to the need for a systematic census and registration of
microcythemics by means of screening all elementary school children, of a vigorous and effective eugenic information
campaign among the microcythemic populations, and the organization and functioning of special marriage counselling
centres”. And he concluded, on the basis of his previous experience with the network of centres coordinated by him,
that “Of course, all these tasks of health care, study and research, census taking, eugenic propaganda and pre-marriage
prophylaxis against Cooley's anemia can be carried out only by ad hoc specialist Centres that guarantee these tasks are
carried out immediately and fully36.
Microcythemia and Cooley's anemia were thus recognized as “pathological forms to be defined
as social diseases” by decree of the Ministry of Health of 20 December 1961. The Ministry of
Health had the task of setting up the relevant health care Centres. In order to be recognized by the
Ministry and have access to the social disease funds, the network of centres set up by Silvestroni
and Bianco nevertheless had to have legal personality. To this end, on 16 November 1961 the
Associazione Nazionale per la Lotta contro le Microcitemie in Italia – ANLMI was set up in Rome,
with its main office at the Institute of Hygiene at the University and with Vittorio Puntoni as
Chairman and Vittorio Del Vecchio as Vice Chairman. On these new bases and finally having been
given a permanent position in Italian health care policy, the work of expanding the network of
microcythemia centres could be resumed. In 1963, a nine-year convention stipulated with the
Ministry of Health finally guaranteed ANLMI the funds it needed to be able to define a rational
programme of development with some certainty of its duration in time.
In the meantime, during the first Congress held in Rome in May 1961, Silvestroni and Bianco
presented the results of fourteen years of Italy-wide epidemiological campaigns and the analysis of
over 100,000 subjects tested37. Thanks to the abundance of case histories and the collaboration of
the Institute of Probability Calculus of Rome University, Silvestroni was able to postulate the
presence of about 2 million microcythemics in Italy, from whom the birth of 1,000 cases of the
disease per year could be expected. The figures referring to the number of sick persons were
however overestimated as alpha-microcythemia, which does not lead to thalassemia even in
homozygous conditions, was not known at the time.
In those years, however, the extent of another alarming epidemiological phenomenon began to
emerge: the appearance of microcythemia and thalassemia in previously unaffected zones, as the
effect of migratory flows from the areas of origin. As regularly happens in history, the
epidemiological dynamics was associated with economic pressures and needs. In this way it was not
just by chance that the 5,800,000 persons that migrated towards the industrial triangle of MilanTurin-Genoa between 1951 and 1965 mostly came from the microcythemic foci distributed over the
national territory: the Po delta, the southern and island regions. Towards the mid ’60s, the incidence
of microcythemia in the industrial regions of the North practically doubled (compared with the
postwar period38.
4.3
Expansion of the network of centres over Italy
In early 1965 16 such microcythemia centres were in operation in Italy. In the same year the
centres provided care for a total of 1,338 patients, carried out 17,414 medical examinations and
blood tests, performed 5,484 transfusions, and 40,147 miscellaneous tests and screened 76,235
persons for microcythemia.
A root and branch network had thus been created, the first in the world, for the prevention and
treatment of thalassemia. At the beginning of the seventies, Cypriot and Greek governments took
this organization as a model for thalassemia prevention policies. In Cyprus a programme for the
prevention of beta-homozygous thalassemia, founded on public education, population screening,
genetic counselling, started in 197339, while the national Greek programme for thalassemia
prevention began in 197440. Services were provided through the Central Unit of Prevention of the
"Thalassemia Center" affiliated with the "Laikon" Hospital in Athens and 21 "Units of Prevention"
affiliated with hospitals in other towns in Greece, mainly in areas of high prevalence. Like
Silvestroni-Bianco’s, the Greek programme was based on:
1. raising public awareness (through the mass media, articles in the press, education in
schools, posters, a series of leaflets for prospective parents, booklets specifically directed
at high schools for teachers and students)
2. screening tests for the identification of carriers
3. genetic counselling.
4.4
From the State to the Regions: the crisis in the microcythemia centre network
In the early ’70s, just when ANLMI was establishing its model as the prototype for prevention
plans throughout the Mediterranean area, its activity was practically completely blocked by an Act
of Parliament. In 1971, the establishment of the regional organization and consequent
decentralization and transfer of power from the state to the regions meant that the microcythemia
centres would be transferred under the direct authority of the regions. This meant essentially that the
national network created by the ANLMI would be broken up, the coordination of the activities
largely interrupted, together with the exchange of experiences acquired in the various different
areas, and the possibility of any comparison or measurement of the effectiveness and of the
regulation of the preventive action taken in the various Italian thalassemia foci would be impaired.
The consequences are seen to be all the more serious when it is considered that the ANLMI, among
other things, supported almost entirely the prevention of thalassemia and the treatment of Cooley's
anemia patients throughout the whole of Italy41. The microcythemia centre of Cagliari, situated in
the region with the highest thalassemia incidence in Italy, did not open again until January 1975,
when also the Rome centre resumed regular functioning on the basis of a five-year convention
stipulated with the Lazio Region.
5
The construction of the prevention model
Right from the early ’60s, Silvestroni and Bianco were obliged to carry out their
epidemiological research and to try and start up prevention in Italy without any permanent or
productive collaboration (except in the case of Ferrara), with funds that were scanty in proportion to
the task, and often able to count on material help exclusively from some local authorities who were
more sensitive to the problem.
The work of health care information and education, of central importance in the prevention
model, thus ended up by being carried out unsystematically, at the same time as the numerous
screening campaigns carried out in various Italian regions. Together with the health care personnel
that received them locally and accompanied them in their “haematological censuses”, the two,
particularly in public meetings held in schools, verbally passed on information concerning these
diseases and gave advice on how to prevent them. Whenever carriers were identified, their families
were contacted and examined, and so further information was passed on concerning thalassemia,
and the rules for pre-marriage prevention were recommended.
Starting in 1954, with the opening of the Rome microcythemia centre and the subsequent
establishment of the local sections in various Italian cities starting in 1956, their work of
dissemination became more intense. Above all at the level of the locations in which Silvestroni and
Bianco’s work had begun and where the greatest sensitivity had been shown by the local authorities,
the local health authorities and the educational and child care institutions, such as at Ferrara and
Rome, the growth of health care education regarding microcythemia was given a strong impulse.
In 1956, in Ferrara, the systematic screening of the school population was begun, accompanied
by the compilation of a hematological register for the province42. In the early ’60s, under pressure
from the thalassemia emergency, the Municipality of Ferrara, in collaboration with the
microcythemia centre, also opened a pre-marriage counselling bureau. In 1963 the Ferrara
microcythemia centre concluded the screening of the entire school population of the province43.
The identification of carriers at school led to the investigation being extended to entire family
groups and thus to the compilation of personal records drawn up for the provincial hematological
archives. The family was thus able to receive preliminary genetic counselling in the form of a
written communication couched in very simple and clear terms and of an interview. The counselling
was aimed at “creating a pre-marriage eugenic mind set”44.
Health care education was given at school, in preparation for the microcythemia test days, in the
pediatric consulting rooms of the Opera Nazionale Maternità e Infanzia – ONMI (National
Maternity and Childhood Organization), directly in the microcythemia centres and consulting
rooms, by means of printed material and individual interviews, and meetings with entire family
nuclei. Starting in 1956, microcythemics identified in the school screening programme began to
receive a pro-memoria in the form of a card describing their status of carrier, and accompanied by
several precise pre-marriage eugenic indications45.
This root and branch information work actually led to an appreciable increase in the level of
eugenic awareness of the Ferrara population. This is shown by the increased demand for
microcythemia testing at the centre also from young people and engaged couples46.
To a lesser degree than in Ferrara, the elementary school screening tests were carried out by all
the other ANLMI microcythemia centres. From the end of the war until the mid ’60s, in a period in
which the mass media and the health care information received by the population in general had
little effect, and medical and health care personnel lacked training in dealing with the disease, they
certainly represented one of the most effective means for reaching and informing also the adult
population.
It was attempted to use the compulsory state school system to carry out pre-census and intracensus popularising campaigns, with meetings and letters to parents requesting permission to carry
out the tests, and sensitising the teachers. As would be expected in view of the logic specific to the
preventive approach, measurable prophylactic effects were long in coming. Over the years it
became clear that screening the children at school was comparatively ineffective. The very young
age of the subjects made the transmission and comprehension of the educational content difficult, as
well as its use, in view of the complexity of the message and the fact that its object was to prevent
individual behaviour that would occur only many years later. Furthermore, the information on the
carrier’s status was abstract and perceived only fleetingly even by adult individuals.
Consequently, towards the mid ‘60s, the ANLMI further attempted to gear the action to age
groups and the specific population. With the collaboration of the municipalities and marriage
counselling bureaus, it was attempted to intercept the population at a fertile age and about to
reproduce. In several Italian regions, the microcythemia centres began yearly to distribute printed
information material to the marriage registry offices of the local administrations, to be distributed to
couples gathering the documents they needed to get married.
In May 1967, the Rome microcythemia centre began screening students at Rome University. By
1975, the year in which the Centre, finally funded in an appropriate manner, began the programme
of systematically screening school pupils in the final year of secondary school in the Lazio Region,
about 47,000 university students had undergone microcythemia tests and received information and
sometimes genetic counselling47.
After 1975, following the indications of the Rome microcythemia centre, the screening of
pupils, aged about 13 years, attending the final year of compulsory schooling was begun in regions
with the highest incidence of thalassemia. Annual screening and the preparatory and educational
action associated with it resulted in increased awareness of the problem and of the rules for
preventing it, a chain dissemination of the information which then led to a considerable increase in
the demand by young people of child bearing but post-school age and young married couples
(which tripled between 1975 and 1980)48.
6
Debate and controversy regarding the prevention of thalassemia
The measure of the scant consideration given to the problem of thalassemia in Italy is
eloquently expressed by the lack of vivacity of the debate on prevention in scientific circles at both
the political and the cultural level. The rare occasions of stimulus to analysis and discussion of
methods of the research, treatment and prevention of thalassemia, at least up to the mid ‘70s, came
solely from Silvestroni and Bianco and their association through the organization of periodic
lectures on the topic and articles in the scientific press.
Few controversial issues thus arose out of the obstacle-ridden action of prevention promoted by
ANLMI in spite of the importance and heterogeneous nature of the problems it raised at different
levels – genetic, health care, ethical and political.
6.1
Other prevention hypotheses
The sporadic action taken in those years included also other proposed preventive measures.
From the early ‘50s on it was a commonly held idea that the migration of individual microcythemic
family groups should be encouraged away from microcythemic areas to non microcythemic areas,
as well as the opposite, that is migration of normal family groups to thalassemic areas49. However,
epidemiological and social research carried out on immigrants from microcythemic zones to the
industrial settlements in northern Italy had, as early as 1965, demonstrated the scanty benefits and
even the detrimental effects of such measures. Inside the immigration areas there was a clear-cut
trend towards selective marriages, with a prevalence of marriages between persons from the same
origin which thus led to an increase in the probability of thalassemic carriers and thus to the birth of
children suffering from Cooley's anemia50. In this sense, the thinking related to the prevention
policies to be implemented in the northern regions began to include variables, factors and activities
of a social, economic and town planning nature, such as the problem of the local integration of
immigrants, their distribution over the territory and therefore the placement of the popular housing
and industrial settlements51.
6.2
The position of the Roman Catholic Church
The Roman Catholic Church took only a marginal interest in the prevention of thalassemia,
even though the prophylactic campaign undertaken by Silvestroni and Bianco and the other
preventive measures proposed raised a series of moral issues and were based on measures aimed at
interfering with individual reproductive choices and were thus in conflict with Roman Catholic
doctrine and values.
In general, the Church displayed no organic thinking or reaction to the prevention campaign. In
our opinion this is clear evidence of the limited spread of the plan deployed by ANLMI in the
country and in Italian society as a whole, that is, of the pragmatic response by the Church in those
areas in which this action instead attained a higher level of intensity and penetration among the
population, such as Ferrara. However, also in this case it would be necessary to gauge the different
degree of religious feeling revealed in the customs of the different Italian regions in the
implementation and effectiveness of the prevention programme attempted before the introduction of
prenatal diagnosis. We mention en passant the limited effectiveness of prevention in the province of
Rovigo, where Catholic culture had a strong hold, compared with Ferrara, an area marked by
pronounced laicism and a culture often in open dispute with the Church.
A direct interest in the prevention of thalassemia was however shown by the Pope, Pius XII. On
12 September 1958, Pope Pacelli, at a special audience at Castel Gandolfo, received the participants
at the VII Congress of the International Hematology Society, and gave a speech in which he
presented the Church’s position concerning the possible solutions “to the problem of defective
inheritance” and in particular how to approach “genetic counselling”. Pius XII gave explicit
answers to a series of questions that he was asked by hematologists and geneticists, four of which
referred precisely to the moral dimensions of the Mediterranean anemia prevention campaigns. To
the question concerning the moral legitimacy of recommending a pre-marriage medical examination
and blood test, the Pope replied that not only was it to be recommended but
if the danger is truly serious [the visit and examination] could even be imposed in certain provinces and locations52
Only a thorough assessment of all the facts, such as to reveal the seriousness of the situation,
would however legitimate an ethical edict. To the question whether it was “allowed to recommend
that two fiancées should not marry if a blood test revealed the presence of Mediterranean anemia”53,
the Pope repliced that it was possible to advise against the marriage but not prevent it. Regarding
the legitimacy of advising against a married couple with Mediterranean anemia having children, the
Pope replied to the scientists that they could be advised against it but not forbidden. And in any case
it was necessary to decide what method was to be used, since for the Church only “perfect
continence”, “the Ogino-Knaus method”, or “the adoptioon of children” were acceptable. The Pope
then reiterated that the discovery that one of the couple was affected by Mediterranean anemia
could not be considered a reason for annulment of the marriage, even if the relevant information
had been withheld.
In practice, - Pius XII concluded – it will often be difficult to reconcile the two points of view – eugenic and
moral. But to guarantee the objectivenenss of the debate it is necessary for each to know the other’s point of view and to
be familiar with the arguments54.
6.3
The dysgenic effects of prevention
One of the topics of discussion was that of the dysgenic effects of prevention. It was objected
that primary prophylaxis carried out by restricting marriages between carriers would ultimately
increase the prevalence of microcythemia 55.
As Alicino and Fabiani wrote:
It is thus possible to implement a primary prophylaxis against Cooley's anemia by restricting marriage between carriers.
However, this concept lends itself to criticism from the purely genetic point of view. By so doing, we actually
encourage the spread of microcythemia. Indeed, according to Mendel’s laws, the mating of two individuals
heterozygous for microcythemia will produce a descendance of which one quarter is homozygous. Homozygotism is
however incompatible with life and reproduction: the inherited defect will in some cases be eliminated. Mating the
heterozygote with a normal individual favours conservation of the defect. Consequently, in order to eradicate
microcythemia it would be necessary to encourage marriages between individuals with hereditary defects. However,
this concept is repugnant to our conscience as physicians as well as as men, and so it is necessary to approach the
campaign against microcythemia by endeavouring to avoid the disease at the state of homozygotism56.
There was concern about the high cost and the difficulty of exerting constant control over the
prevalence of carriers and of a continual expansion of prevention activities. Running counter to this
concern was the hypothesis of malaria as a selective factor in favour of carriers57. In this sense, in
1973, at V Congress on Microcythemia held at Cosenza Ida Bianco claimed:
clearly the recent land reclamation and the consequent disappearance of endemic malaria must already have broken
the gene equilibrium among populations, and led to a tendency towards a reduction in the genic frequency of
microcythemia; consequently, the introduction of pre-marriage prophylaxis into this system, which is no longer in
equilibrium but in downward movement, will not succeed in bringing about fresh increases but will at most cause a halt
in the decline of gene frequencies to the present levels58.
Several years later, when reflecting also about the effects of prenatal diagnosis on the human
gene pool, Arno Motulski subjected the problem to detailed discussion. He claimed that the
question of the dysgenic effects was exaggerated but nevertheless drew attention to the need to
disseminate more information about genetics and its medical applications59.
7
On the effectiveness of the Silvestroni-Bianco prevention programme
No special or specific studies have been carried out on the effectiveness of prevention
implemented in Italy in the mid ’50s and the two decades that followed60. In any case, although not
directly observed, as Bianco herself admitted (personal communication) the short-medium term
effects of the prevention action that it was actually possible to carry out were scarce and in some
regions completely non existent.
The small number of works in which it was attempted to evaluate the effects of the ANLMI
prevention programme are however subsequent to the introduction of prenatal diagnosis and to
some extent the victims of the euphoria that led people to believe that the latter method had solved
the thalassemia problem61. The data emerging from retrospective investigations of subjects having
participated in the assessments were successively adjusted. It was noted for example that the
prophylactic model of Silvestroni and Bianco deployed in the ANLMI action had failed to attain its
primary objective: the prevention of marriage between microcythemics62. However, note was taken
of the positive achievements of the ANLMI approach in spreading knowledge of the genetics of
microcythemia and thalassemia63.
Barrai and Vullo showed that the work of screening, counselling, treating and informing carried
out by the ANLMI-coordinated centres was later to be vital also for the purpose of introducing and
spreading prenatal diagnosis64. The population in the areas in which the microcythemia centres had
operated longest and in a systematic, root and branch manner, as in the province of Ferrara,
subsequently proved ready to understand and utilize prenatal diagnosis as soon as this method was
introduced65.
The overall negative judgment on the studies described above fell somewhat acritically into line
with the opinions current at the time, to which priority was given in the international literature on
the topic of mass screening for carriers of recessive gene disorders and marriage counselling66,
above all when they are compared with prevention via prenatal diagnosis67. The negative judgment
passed on mass screening expressed in these studies could however be applied only in part to the
case of thalassemia prevention carried out in Italy between the ’50s and the ’70s. This judgment
was based on the outcome of prevention plans of problematic conception or application.
Stamatoyannopoulos, for example, based his conclusions on the small number of case histories that
were quite peculiar in their sociocultural conditions referring to the pilot programme carried out in
1966 in a small rural town in Greece68. On the other hand, the more detailed one expressed by the
US Committee for Study of Inborn Error of Metabolism was based above all on the observation of
the screening programme for sickle cell anemia in the US black population, a prevention plan that
was serious flawed at the level of educational and information action owing to the difficulty or
incapacity to establish adequate contact with the population at risk69.
A different case, although with the same impossibility of comparing its effectiveness with
Silvestroni and Bianco’s approach, is the one referring to the action carried out by Mike Kaback in
the USA Tay Sachs disease in the Askenazy community, and that against beta-thalassemia on
Cyprus and in Sardinia, based on prenatal diagnosis, which were characterized by technical
resources, funds, organizational structures and political and social support that were unthinkable at
the time Silvestroni and Bianco embarked upon their work69bis.
Within this framework it is necessary to mention a study on the cost-benefit ratio of the
prevention operation carried out by mass screening. One calculation for the province of Sassari
made in 1973 but published only in 1976, that is, at the beginning of the prenatal diagnosis era,
postulated a distinctly favourable ratio between saving and expenditure for the screening of all
children, even assuming that only 30% of carriers would actually choose pre-marriage prevention
and thus avoid a microcythemic partner70.
7.1
The reasons for the lack of effectiveness
In any case the lack of effectiveness of the programme from the point of view of prevention in
the narrow sense is quite evident, although this can easily be explained in historical terms. The
reasons for this low prophylactic efficiency were in any case known already at the time. The report
presented by Luigi Nuzzolillo, director of the Social Medicine Services of the Italian Ministry of
Health on 28 September 1968 at Cagliari during the microcythemia study days organized by
ANLMI and by the Istituto Italiano di Medicina Sociale, is eloquent on this subject71.
The shortcomings are to be attributed to two groups of interacting factors: a) those related to the
organization and functioning of the organizations involved in the prevention and b) those specific to
the human and social environment in which the prevention was being attempted. As far as the first
group of factors was concerned, it should be pointed out in the first instance that, in the field of
prevention, the ANLMI microcythemia centres were working in practically complete isolation, with
totally inadequate or completely nonexistent funding.
There were not enough Centres to cope with the huge areas over which they had to operate and the
extent of the problem, the geographic vastness in which the prevention activity had to be carried out
also because of the widespread nature of migration-produced microcythemia. Furthermore, it was
impossible to coordinate the cooperation between the network of centres and the other health care
bodies in the area of operations (hospitals, local GPs and obstetricians, O.N.M.I. counselling
bureaus, municipal hygiene and labour offices, armed services medical corps, mutual and
previdential health care institutions). In the absence of specific regulations, these relations were set
up only through the initiative and determination of individuals, above all in those areas in which the
administrators and health care workers were more sensitive. Lastly, the initiatives associated with
mass screening or the health care education and hygiene information campaigns had to cope with
obstacles of an ethical, religious, economic or local custom nature, accompanied by culture-related
distrust and impediments and lack of support from the local political and health care authorities.
Moreover, in this case, it was impossible to develop a common strategy as the socio-cultural
contexts in the various parts of Italy in the early ‘60s in which the various ANLMI personnel were
obliged to operate all differed too strongly.
This last point is worth stressing. The difficulties encountered during the work to raise the level
of awareness and knowledge of the population were indeed too numerous and different. This was
instead of central importance in the plans to prevent genetic diseases, which seem to work only
when accompanied by powerful information campaigns72.
7.2
Long-term effects
A Ministry of Health survey carried out in 1994 shows that the effects of the screening and
prophylaxis work, the dissemination of knowledge – although not in a systematic, root and branch
manner – may be measured by the different rates of effectiveness achieved starting in 1975, after
the introduction of prenatal diagnosis. The reduction of the incidence of thalassemia measured in
the periods 1970-1974 and 1988-1992 shows that the regions with the highest rates of efficiency
were those, like Emilia Romagna and Lazio (in these two cases in 1992 a zero rate of birth of new
sufferers of the disease was attained), where the work of screening and of the dissemination of
information about the disease had been carried on longest, together with the dissemination of the
idea of pre-marriage prevention73.
The different degree of sensitivity to prevention is actually measurable inside the same region
and thus theoretically under very similar socio-economic conditions, at the same levels of
education, prophylactic and educational action from 1975 on. Thus, in Ferrara, with an 8%
prevalence of heterozygotes, no homozygotes have been born since 1982; on the other hand, over
the same period, new cases of the disease were recorded in the rest of the Emilia Romagna region,
where heterozygous prevalence is only as high as 1%74.
And this is not all. Over the same period of time, with the same level of care and therapy, the
regions with a more consolidated prevention experience and a more widely disseminated knowledge
of the problem at the population level - again Emilia Romagna and Lazio – boast a greater
extension of the average life of the patients, up to five years longer than in the other regions with
high thalassemia incidence75.
Other studies on Mediterranean anemia mortality studies in Italy during the period 1951-1976
recorded by the Istituto Centrale di Statistica (ISTAT), reveal a clear-cut reduction in thalassemia
mortality starting from 1965, with an incidence of 0.60 out of 100,000 inhabitants, to 0.26 in 1976,
is probably a reflection on the improvement in the diagnostic systems, the treatment and the care of
Cooley’s anemia patients76.
The Mediterranean anemia mortality figures for the first year of life presented in the study seem
to be particularly significant for the purpose of making a positive assessment of eugenic and
preventive action, of the refresher training of healthcare personnel and of the raising of the level of
awareness of the population priort to the introduction of prenatal diagnosis. From 1965 to 1976 this
mortality rate dropped from 6.26 to 1.02. The decrease, the equivalent of a 7.4 fold reduction, was
distinctly higher than that recorded over the same period of time of infantile mortality as a whole,
which corresponded to 1.9 times77.
Some indication of the preventive efficiency of Silvestroni and Bianco’s approach also comes
from the data referring to the mortality trends of Mediterranean anemia broken down by province.
In the provinces of Ferrara and Rome the decline in the mortality rate began in the late ’50s, nearly
ten years earlier than in the rest of Italy, and progressed very rapidly. Within 5-10 years, constant
minimum levels were reached78.
8
Conclusions
The work by Silvestroni and Bianco, the mass screening and the premarriage prevention carried
out by ANLMI took place in a period in which genetic medical knowledge was at a low level, to say
the least, also among physicians, a period in which the average educational level of the Italian
population was low, and their cultural, moral and ethical resistance to the use of the already
fragmentary notions of prevention obtained by means of genetic counselling much higher than they
are today. The diversity of cultures and customs among the various Italian regions was, in a word,
very pronounced.
In some ways, the low level of health care education attained, the slowness of the penetration of
the messages conveyed by the prevention campaigns, the partial adjustment over time of the level of
education and thus of the understanding of the content of the information campaign, made the
eugenic appeals and the use of the prevention centres less traumatic and fraught with conflict. This
differed from the case of Cyprus where the widespread information, repeated and intensive, at root
and branch level, where the combined coordination efforts of the lay and religious organizations
and of the health care authorities directed towards a massive appeal to prevention, created a
dominant opinion and such strong social pressures that the desired behaviour was actually imposed,
and non directive genetic counselling was rendered unlikely79.
Although unable to modify the behaviour of individuals in the short term, this disseminated
knowledge, metabolised by several generations of Italians through the ANLMI prevention plan,
rendered the prevention choices more conscious and thus freer when prenatal diagnosis became
available. It also made it possible to tackle with a higher degree of maturity the inevitable tension
between the quest for individual wellbeing, the realization of personal values and health care
policies addressed to the community and to the State’s needs: this tension increases when
prevention campaigns are run.
For all these reasons, probably, the assessment of the experience of the ANLMI prevention plan
must be expressed in a broader time span, considered over a longer period of time. It is thus
necessary rather to interpret the prevention plan coordinated by Silvestroni and Bianco as marking a
beginning, the beginning of one of the most complex preventive medicine operations ever carried
out in Italy and to some extent in the world, preparing the way for the later action.
It will be the subject of a later work to compare, as far as possible, the results obtained at the
quantitative and qualitative level (the latter defined as the degree of cultural awareness of the
population regarding the problem and effectiveness of counseling) by Silvestroni and Bianco
through the screening work and campaigns carried out in Sardinia by Antonio Cao exclusively by
means of prenatal diagnosis. We can already advance some conclusions by pointing out that after
the initial acritical enthusiasm, the prospective prevention programme using prenatal diagnosis
begun in Cagliari in September 1977, after a few years showed some signs of weakness and the
indubitably high efficiency of the action did not come up to initial expectations. On the one hand,
the approach sometimes actually failed to prevent unidentified couples at risk from giving birth to
new cases of the disease; on the other, precisely the behaviour of the couples at risk, after the
introduction of prenatal diagnosis, tended partially to clash with the preventive effects of the
method. The phenomenon of “compensatory reproduction”, that is, the observed fact that couples
with children suffering from the disease gave birth to twice as many other children as carrier
couples with healthy children, is indicative of the need in prevention programmes to proceed along
the path of screening so as to be able to carry out true prospective prevention80. In pratice, precisely
by working on the idea that prenatal diagnosis is sufficient to prevent the birth of homozygotes,
Cao’s group discovered – although it failed to assign to it the importance it deserved – that the birth
of a child with the disease seems to have deterrent effect, above all on adequately informed couples.
Both in prevention achieved by voluntary limitation of births and in that attained via prenatal
diagnosis, information is of fundamental importance. Just as Silvestroni and Bianco always
maintained.
BIBLIOGRAPHY AND NOTES
1. As James Neel points out, the reason why the prevention programmes proved so effective in
Sardinia and on Cyprus is because “about 95% of the defective alleles result from the same
mutation”. NEEL J.V., Physician to the Gene Pool. Genetic Lessons and Other Stories, John Wiley
& Sons, New York, 1994, p. 365.
2. ANIONWU E.N., ATKIN K., The politics of sickle cell and thalassaemia. Open University
Press, Buckingham – Philadelphia, 2001.
3. With the advent of prenatal diagnosis and the consequent option of selective abortion, the use of
the concept of "prevention" of genetic diseases through the state-organized screening of populations
was criticized in that it might contain elements of directiveness regarding the counselling and imply
a eugenic dimension through the direct and indirect influence of the health care objectives. For an
analysis of the conflict between the idea of prevention underlying screening for genetic diseases at
the population level and the idea of “informed decision-making”. ANIONWU E.N., ATKIN K., ref.
2, pp. 46-53.
4. Italy is the European country with the greatest increase in the number of genetic tests and with
the largest number of molecular diagnosis laboratories. A recent study by the Società Italiana di
Genetica Umana (Italian Society for Human Genetics) voiced its concern that this increase has not
corresponded to an improvement in the quality of information given to users or in the training of
physicians; in other words, "the inadequacy, or more frequently, the total lack of counselling, which
must, or rather should, be part and parcel of genetic tests ”. See DALLAPICCOLA B., TORRENTE
I., MARI A., MINGARELLI R., Censimento dei test genetici in Italia. Anno 2001. Società Italiana
di Genetica Umana, 2001, Roma.
5. WHIPPLE G.H. AND BRADFORD W.L., Racial and familial anemia of children. American
Journal of Disease of Children 1932; 33: 336-65; WHIPPLE G.H., BRADFORD WL.,
Mediterranean disease – thalassemia (erythroblastic anemia of Cooley): associated pigment
abnormalities simulating hemochromatosis. Journal of Pediatrics 1936; 9: 279-311.
6. COOLEY T.B., LEE P., Erythroblastic anemia. American Journal of Disease of Children 1932,
43: 705-8.
7. LEHNDORF H., Die Erythroblastenanämie. Ergebn. Inn. Me. U. Kinderh. 1936; 50: 568.
8. ANGELINI V., Primi risultati di ricerche ematologiche nei famigliari di anemia di Cooley.
Minerva Medica 1937; 28: 331-2. MICHELI F., PENATI F., MOMIGLIANO LEVI G., Anemia
ipocromica splenomegalica con ellittocitosi-poichilocitos. Atti e Memorie della Società Lombarda
di Medicina 1935; 3: 739-752, seduta del 12 aprile 1935. MICHELI F., PENATI F.,
MOMIGLIANO LEVI G., Ulteriori ricerche sulla anemia ipocromica splenomegalica con
ellittocitosi-poichilocitosi. Haematologica 1935; 16, 10: 5-9. CAMINOPETROS J., L'anémie
erythroblastique des peuples de la Mediterranée orientale. Monogr. Acad. Athènes 1937; 6, 3, pp.
81-141.
9. WINTROBE M.M., MATHEWS E., POLLACK R. AND DOBINS B.M., A familial hemopoietic
disorder in Italian adolescent and adults resembling Mediterranean disease (Thalassemia). Journal
of American Medical Association 1940; 114: 1530-38. DAMESHEK W., Target cell anemia.
Anerythroblastic type of Cooley’s erythroblastic anemia. Am. J. med. Sci. 1940; 200: 445-54.
10. CAMINOPETROS J., ref. 8, p. 124.
11. MONCRIEFF A., WHITBY L.E.H., Anemia of Cooley. Lancet 1934, 2: 648.
12. GATTO I., Ricerche sui familiari dei bambini affetti da malattia di Cooley. Rivista di Clinica
Pediatrica 1941; 14, 5: 225-252. GATTO I., Ricerche sui familiari dei bambini affetti da malattia di
Cooley. Archivio Italiano di Pediatria e Puericultura 1942; 9: 128-168.
13. SILVESTRONI E., BIANCO I., Prime osservazioni di resistenze globulari aumentate in
soggetti sani e rapporto fra questi soggetti e i malati di cosiddetto ittero emolitico con resistenze
globulari aumentate. Bollettino e Atti della Accademia Medica di Roma 1943; 69, 11: 165-181,
seduta del 26 novembre 1943. SILVESTRONI E., BIANCO I., Microcitemia e morbo di Cooley.
Bollettino e Atti dell’Accademia Medica di Roma 1945; anni accademici 1945-46: 3-4, sessione del
29 December 1945. SILVESTRONI E., BIANCO I., Ricerche sui familiari sani di malati di Morbo
di Cooley. Ricerche di Morfologia 1946, 22.
14. SILVESTRONI E., BIANCO I., Ricerche sull’eziopatogenesi del morbo di Cooley. Minerva
Medica 1946; II, 91. SILVESTRONI, E., BIANCO, I., Nuove ricerche sui famigliari di malati di
morbo di Cooley e prime osservazioni sulla frequenza dei portatori di microcythemia nel ferrarese
e in alcune regioni limitrofe. Bollettino ed Atti dell’Accademia Medica di Roma 1946-1947; 72, 32,
anni accad., 1945-46, 1946-47, p. 1.
15. SILVESTRONI, E., BIANCO, I., Nuove ricerche sulla trasmissione ereditaria della
microcitemia. Policlinico Sez. Prat. 1947; 54: 1359-1363
16. DAMESHEK W., Familial Mediterranean target-oval cell syndromes. Am. J. med. Sci. 1943;
205: 643-60.
17. NEEL J.V. E VALENTINE W.N., Hematological and genetic study of the transmission of
thalassemia (Cooley’s anemia, Mediterranean anemia). Archive of Internal Medicine 1944; 74:
185-196. Vlentine & Neel, 1945). VALENTINE, W.N., NEEL, J.V., The frequency of thalassemia.
Am. J. Med. Sci. 1945; 209: 568-72.
18. The Italian medical literature of this period on the subject is extremely vast and provides
evidence of the great difficulty encountered, even when there was no conceptual resistance, in
identifying thalassemia minor within the broader framework of the thalassemic diseases and to
understand the genetic relationships among the various symptoms (for a detailed review, see:
SILVESTRONI E., Microcitemia e malattie a substrato microcitemico. Falcemia e malattie
falcemiche. In Atti del 50° Congresso della Società Italiana di Medicina Interna, Ed. Pozzi, Roma,
1949, pp. 108-298. ASTALDI G., TOLENTINO P., SACCHETTI C., La thalassemia. Tipografia
del Libro, Pavia, 1951. BANNERMAN R.M., Thalassemia. A survey of some aspects. Grune &
Stratton, New York, 1961.)
19. In a moving autobiography soon to be published (Storia della Microcitemia in Italia. Pagine di
Scienza e di Vita, Fioriti Editore, Roma), Ida Bianco gives a detailed description of the humiliations
endured as the result of a conception of academic power interpreted as the absolute and unflinching
domination by directors of the university institutes.
20. SILVESTRONI, E., BIANCO, I., reff. 14 and 15. SILVESTRONI E., BIANCO I., Sulla
frequenza dei portatori della microcythemia nel Ferrarese, sui gruppi sanguigni dei microcitemici
e sulla trasmissione ereditaria della microcitemia. La Ricerca Scientifica 1947; 17: 2021.
SILVESTRONI E., BIANCO I., Sulla frequenza della microcitemia nel Ferrarese e in alcune altre
regioni d’Italia. Policlinico, Sez. Prat. 1948; 55: 417. SILVESTRONI E., BIANCO I., Nuove
ricerche sull’eziologia del morbo di Cooley e prime osservazioni sulla frequenza della
microcitemia nel Ferrarese. Minerva Medica 1948; 39, 1: p. 8. SILVESTRONI E., BIANCO I.,
Sulla frequenza della microcitemia in alcuni paesi della Puglie. Minerva Medica 1948; 39, 1: 232.
SILVESTRONI E., BIANCO I., Sulla frequenza della microcitemia nel Ferrarese e in alcune altre
regioni d’Italia. Policlinico Sez. Prat. 1949; 56: 906. SILVESTRONI E., BIANCO I., Ricerche
sulla frequenza della microcitemia in alcune città dell’Italia continentale. Bollettino e Atti
dell’Accademia Medica di Roma 1949c, anni accademici 1948-49, 74: 28. SILVESTRONI E.,
BIANCO I., Sulla frequenza della microcitemia in varie città e regioni d’Italia. Policlinico, Sez.
Prat. 1949d; 56 : 602. SILVESTRONI E. AND BIANCO I., MONTALENTI G., SINISCALCO M.,
Frequency of Microcytemia in some italian district. Nature 1950; 165: 682.
21. SILVESTRONI E., BIANCO I., Il metodo Simmel per lo studio delle resistenze globulari
aumentate. Policlinico Sez. Prat. 1945b; 51: 153. The test was based on two observations:
measurement, in a single hypotonic saline solution, of the increase in erythrocyte osmotic
resistance; the identification of any morphological alterations of the erythrocytes on uncoloured
blood smears. This method became the standard diagnostic procedure owing to its great reliability
(over 98%) and because of the rapidity with which the test could be conducted, which allowed up to
100 tests per hour to be performed.
22. SILVESTRONI E., BIANCO I., Ricerche sull’eziopatogenesi del morbo di Cooley, ref. 14.
Actually, it was the Greek hematologist, Jean Caminopetros, who first claimed it was possible to
prevent thalassemia, or rather, as it was called at that time, erythroblastic anemia, by forbidding
procreation by carriers. In 1937 he wrote: "L’examen de la résistance des globules rouges constitue
une méthode sure pour trouver parmi les membres des familles des malades, les porteurs
apparemment sains de la maladie, et par ce fait permet la prise de mesures de prophylaxie sociale.
L’interdiction de la procréation, le seul moyen de prophylaxie indiqué contre la maladie, devient
applicable, parce qu’elle peut se limiter à quelques personnes seulement de la famille des malades."
Caminopetros J., ref. 8., p. 139.
23. SILVESTRONI E. ref. 18, p. 235.
24. KAN Y.W., GOLBUS M.S., TRECARTIN R., FURBETTA, M., CAO, A., Prenatal diagnosis
of homozygous beta-thalassaemia. Lancet 1975; 2 (7939): 790-1.
25. SILVESTRONI E., BIANCO I., Nuove ricerche sull’eziologia del morbo di Cooley etc., ref. 20.
26. SILVESTRONI E. ref. 18.
27. In an interview published in Avanti on 19 November 1949, Silvestroni declared: "How is it
possible to prevent a disease for which no cure has yet been discovered? There are two ways,
according to us. One, which involves the State taking on the task of continuing research without
burdening doctors; the other, which impresses upon the people the importance of a feasible
eugenics by avoiding marriages between microcythemics, is thus capable of reducing the cases of
the disease to an insignificant number".
28. Set up in 1945 by Decreto Luogotenenziale 12 luglio 1945, n. 417 and later organized into its
functions and attributions by Decreto legislativo Luogotenenziale 31 luglio 1945, n. 446, the Alto
Commissariato per l’Igiene e la Sanità Pubblica (ACIS) was, until the establishment of the
Ministry for Health in 1958, the main body concerned with the protection of public health, the
coordination and technical monitoring of the health care organizations and the bodies having the
function of preventing and combating social diseases. The ACIS was placed under the control of the
Presidency of the Council of Ministers and enjoyed all the prerogatives previously exercised by the
Ministry of the Interior in the field of hygiene and public health, as provided for in the consolidated
health care legislation approved by Regio Decreto 27 July 1934, no. 1265.
SILVESTRONI E., BIANCO I., Un problema medico-sociale: la microcitemia e il morbo di
Cooley. Annali di Sanità Pubblica 1953; 8: 1439.
29.
30. Source: Ida Bianco Personal Archive – APIB.
31. Measure no. 560/20300/24/68 of 5 August 1954.
32. Letter from Tessitori to Puntoni, 18-9-1954, APIB.
33. ARCHIVIO GIUSEPPE MONTALENTI - AM (1954) Letter dated 22 January 1954 from the
director of the European Office, R.R. Struthers, to Montalenti. B125, Archivio Montalenti, Bib.
Storia della Medicina, Università degli Studi di Roma “La Sapienza”.
34. This was the order of opening: 1956, Ferrara, directed by Marino Ortolani; 1957, Cosenza,
directed by Carlo Brancati; 1958, Palermo and Cagliari, directed respectively by Michele Gerbasi
and Giuseppe Macciotta; 1960, Naples, Reggio Calabria and Lecce, directed respectively by Nevio
Quattrin, Demetrio Meduri and Filippo Muratore. The sections of Naples, Reggio Calabria and
Lecce, actually began operating only towards the end of 1961, because of the serious delays in
actual disbursement of the allocated funds, which nearly led to the collapse of the entire network of
Centres, including that of Rome. In this connection see the letters written by Silvestroni, by the
director of the Institute of Hygiene, Vittorio Del Vecchio and by the Head of the Faculty of
Medicine, Vittorio Puntoni to the Minister of Health, Camillo Giardina and the latter’s replies.
Source: APIB.
35. Report by Silvestroni to the Consiglio Superiore di Sanità, Session XXXI, Section I, Meeting of
5-12-1961, 9 a.m. Source: APIB.
36. Report by Silvestroni to the Consiglio Superiore di Sanità, Session XXXI, Section I, Meeting of
5-12-1961, 9 a.m. Source: APIB
37. SILVESTRONI E., BIANCO I., Diffusione e frequenza della microcitemia e delle anemie
microcitemiche nell’Italia continentale e in Sicilia. In Atti delle Giornate di Studio sul problema
sociale della microcitemia e del morbo di Cooley, Istituto Italiano di Medicina Sociale, Roma,
1961, pp. 138-159.
38. POLLI E., BESTETTI A., ROSSI U., Aspetti sociali della microcythemia nelle zone industriali
del Nord Italia, oggi. La provincia di Milano. In Atti delle Giornate di Studio sulla Microcythemia.
Ferrara – 23-24 October 1965, Istituto Italiano di Medicina Sociale, Roma, 1965, pp. 81-97
SANSONE G., Aspetti sociali delle microcitemie nelle zone industriali del Nord Italia, oggi. La
provincia di Genova. In Atti delle Giornate di Studio sulla Microcitemia , Ferrara – 23-24 October
1965, Istituto Italiano di Medicina Sociale, Roma, 1965, pp. 97-103.
39. ANGASTINIOTIS M.A., HADJIMINAS M.G., Prevention of thalassaemia in Cyprus. Lancet
1981; 1, 8216: 369-71.
40. LOUKOPOULOS D., KALTSOYA-TASSIOPOULOU A., FESSAS P., Prevention of
thalassemia. Schweiz Med Wochenschr 1983; 113, (40): 1419-27.LOUKOPOULOS D.,
KALTSOYA-TASSIOPOULOU A., FESSAS P., Thalassemia control in Greece. Birth Defects
Orig Artic Ser. 1988; 23 (5B): 405-16.
41. NUZZOLILLO L., Prospettive organizzativo-sanitarie in rapporto alle nuove conoscenze sulla
epidemiologia microcitemica. In Atti delle Giornate di Studio sulla Microcythemia , Cagliari, 27-28
settembre, Istituto Italiano di Medicina Sociale, Roma, 1968, pp. 413-426.
42. ORTOLANI M., Funzionamento ed attività di un’organizzazione sanitaria distrettuale per la
lotta contro le malattie microcitemiche. In Atti delle Giornate di Studio sul Problema Sociale della
Microcitemia e del morbo di Cooley. Roma Maggio 1961, Ed. Istituto Italiano di Medicina Sociale,
Roma, 1961. LUCCI R., Il contributo dell’O.N.M.I. nella lotta contro la microcitemia in provincia
di Ferrara. In Atti delle Giornate di Studio sulla Microcythemia, Ferrara – 23-24 October 1965,
Istituto Italiano di Medicina Sociale, Roma, 1965 p. 180.
43. SCANDURRA S., BELLODI L., CARACENI B., L’attività del centro della microcitemia di
Ferrara nell’ultimo quinquennio, In Atti delle Giornate di Studio sulla Microcythemia, Ferrara –
23-24 October 1965, Istituto Italiano di Medicina Sociale, Roma, 1965, pp. 235-240.
44. Ib.
45. The wording printed on the microcythemic’s card issued by the ANLMI microcythemia centres
ran as follows: “……. is a carrier of microcythemia, a slight hereditary blood disorder. There is no
cause for alarm: he is not sick and will always be able to enjoy good health. However, he must be
careful about marriage! He must marry a non microcythemic woman. If he married a
microcythemic woman they might give birth to children who are doomed to die after a few years
from a serious blood disease. So when he gets engaged he will have to have his fiancée take a test at
a specialized laboratory to make sure she is not microcythemic: only when he has been reassured on
this point can he get married without any worries. Then he will have to remember that also his
children could have the same kind of blood as he does: he will therefore have them tested too so
that they too will know what to do before getting married”. Source: APIB.
46. SCANDURRA S., BELLODI L., CARACENI B., ref. 43.
47. SILVESTRONI E., BIANCO I., Screening for microcythemia in Italy: analysis of data
collected in the past 30 years. Am J Hum Genet 1975; 27 (2): 198-212.
48. BIANCO I., GRAZIANI B., LERONE M., PONZINI D., ALIQUÒ M.C., FOGLIETTA E.,
Updated results of the thalassaemia prevention carried out in Latium. J. Med. Gen 1989; 26: 667.
BIANCO I., GRAZIANI B., LERONE M., PONZINI D., ALIQUÒ M.C., AMATO A.,
FOGLIETTA E., CAPPABIANCA M.P., Un modello di intervento globale di prevenzione
dell’anemia mediterranea. In La Prevenzione dell’anemia mediterranea in Italia, oggi. Congress
Proceedings – Rome, I October 1994, Istituto Italiano di Medicina Sociale Editore, 1995, Roma, pp.
23-28. SILVESTRONI E., BIANCO I., Education, screening, and genetic counselling in
thalassaemia. Br Med J 1980a, 12; 281, 6233: 149.
49. LATTE B., Aspetti medico-sociali delle microcitemie in Sardegna. In Atti delle giornate di
studio sulla microcitemia. Cagliari, 27-28 settembre 1968, Istituto Italiano di Medicina Sociale,
Roma, 1968, pp. 407-412.
50. POLLI ET AL.; SANSONE, ref. 38.
51. POLLI ET AL., ref. 38.
52. PIO XII, Discorsi ai medici. Edizioni “Orizzonte Medico”, Roma, 1959, pp. 710-13).
53. Ib.
54. Ib.
55. ALICINO, R. AND FABIANI, M., Aspetti dell’organizzazione della prevenzione della
microcitemia in Italia. In Atti delle Giornate di Studio sulla Microcythemia. Ferrara – 23-24
October 1965, Istituto Italiano di Medicina Sociale, Roma, 1965; LATTE B., ref. 49.
56. ALICINO AND FABIANI, ref. 55, p. 110
57. HALDANE J.B.S., Disease and evolution. Ricerca Scientifica (suppl.), 1949; 19: 3-10;
CEPPELLINI R., Discussion of paper by A.C. Allison on polymorphism in man. Cold Spring
Harbor Symposium on Quantitative Biology 1955; 20: 252.; CARCASSI U., CEPPELLINI R.,
PITZUS F. Frequenza della thalassemia in quattro popolazioni sarde e suoi rapporti con la
distribuzione dei gruppi sanguigni e della malaria. Bollettino dell’Istituto Sieroterapico di Milano
1957; 36: 207-218. CARCASSI U., CEPPELLINI R., PITZUS F., Aspetti attuali della thalassemia
alla luce delle ricerche condotte in Sardegna. In Proceedings of VII International Congress of the
International Society of Hematology. Il Pensiero Scientifico Editore, Roma, 1960. SINISCALCO
M., BERNINI L., LATTE B. Favism and thalassaemia in Sardinia and their relationship to
malaria. Nature, 1961, 190: 1179-1180. MOTULSKY A.G.: Hereditary red cell traits and malaria
Am. J. Trop. Med., 1964, 13: 147-158.
58. BIANCO I., GRAZIANI B., MARINI G.P., La profilassi delle malattie microcitemiche. In Atti
del V Congresso sulle microcitemie. Cosenza 4-5-6 Ottober 1973, Istituto Italiano di Medicina
Sociale, 1976, Roma, p. 529.
59. MOTULSKI A., Impact of genetic manipulation on society and medicine. Science 1983, 219:
135-40.
60. One reason for this lies in the fact that there are no available data on the number of those
suffering from the disease when the difficult undertaking began. Another reason is probably to be
sought in the relative lack of interest shown by the scientific community in the activity of a private
association completely separate from the academic world. Furthermore, the progress of the ANLMI
programme must have been so atypical due to the degree and the mainly low intensity of its
implementation, the involvement and coordination of the institutions and the population in the
various provinces in which it was activated in Italy as not to give at the time the impression of a
univocal and comprehensive plan, a precise preventive action, which could be characterized as a
whole and thus its effectiveness measured. This was due also to the lack of funds and the absence of
involvement of the central health institutions. The lack of support from the health care policies must
however be judged against the background of the general historical context in which it was situated,
in which the preventive approach to genetic diseases had yet to be fully introduced and in which
medical circles themselves did not have a clear understanding of the pathology and mechanisms of
hereditary transmission. See SANSONE G., ref. 38. Another factor was Silvestroni and Bianco's
isolation in the scientific community and consequently their greater difficulty in establishing
contact with and in influencing the centres of control, orientation and funding of health care policy
and research.
61. VULLO C., CRISTOFORI G., SALSINI G., BARRAI I., Considerazioni sul consultorio
genetico nella talassemia. Prospettive in Pediatria 1977; 27: 203. BARRAI I., VULLO C., Genetic
counselling in beta thalassemia in Ferrara. J Genet Hum 1980; 28 (2): 97-104. BARRAI I.,
VULLO C., Screening for beta-thalassemia heterozygotes. Lancet 1980; 2 (8206): 1257. BARRAI
I., VULLO C., Assessment of prospective genetic counseling in the Ferrara area. Am J Med Genet
1980; 6 (3): 195-204. MOLLICA F., MUSUMECI S., ROMEO M.A., DI GREGORIO F. RUSSO
A., SCHILIRÒ G., Consiglio genetico nel centro delle talassemie della Clinica Pediatrica di
Catania. In Bianco, I. (ed.), La prevenzione delle malattie microcitemiche. Atti del VI Congresso
Internazionale, Edizioni Minerva Medica, Torino, 1980, pp. 307-310.
62. In the married group, in fact, the proportion of those having married another carrier was in
agreement with random mating expectations. So, after population screening, it was found that the
individuals identified as heterozygotes knew, in a large percentage, what their state was and what its
possible reproductive consequences were. However, the effect of such knowledge was not
significant in influencing the marriage choice of heterozygotes. See VULLO C. ET AL., ref 61;
BARRAI I., VULLO C., Genetic counselling in beta thalassemia in Ferrara, ref. 61.
63. In a group of 613 heterozygotes for beta thalassemia (267 married, 346 unmarried) who were
screened, mostly at elementary school age, interviewed at the average age of 23.7 years to assess
their knowledge of the heterozygous state and its implications, it was found that 83% recalled
information about their heterozygous state and 60% understood the meaning of being heterozygous.
BARRAI I., VULLO C., Assessment of prospective genetic counseling in the Ferrara area, ref. 61.
64. Ib.
65. BARRAI I., VULLO C., Screening for beta-thalassemia heterozygotes, ref. 61.
66. STAMATOYANNOPOULOS G., Problems of screening and counseling in the
hemoglobinopathies. In Motulsky, A.G., Lenz, W., Proceedings of IV International Conference on
Birth Defects – Wien, Excerpta Medica, Amsterdam, 1973. NATIONAL ACADEMY OF
SCIENCES Genetic screening: programs, principles, and research. U.S. Government Printing
Office, Washington D.C., 1975.
67. KABACK M.M., ZIEGER R.S., REYNOLDS L.W., SONNERBORN M., Approach to the
control and prevention of Tay-Sachs disease. Prog Med Genet. 1974; 10: 103-34. KABACK M.M.,
Medical genetics: an overview. Pediatr Clin North Am. 1978; 25, 3: 395-409. Editorial, Population
screening for carriers of recessively inherited disorders. Lancet 1980; 2, 8196: 679-80. CAO A.,
FURBETTA M., GALANELLO R., MELIS M.A., ANGIUS A., XIMENES A., ROSATELLI C.,
RUGGERI R., ADDIS M., TUVERI T., FALCHI A.M., PAGLIETTI E., SCALAS M.T.,
Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in
Sardinia. Am J Hum Genet 1981; 33, 4, 592-605. ANGASTINIOTIS M.A., HADJIMINAS M.G.,
ref. 39.
68. STAMATOYANNOPOULOS G., ref. 66.
69. NATIONAL ACADEMY OF SCIENCES, ref. 66.
69bis KABACK M.M., O’BRIEN, J.S., Tay-Sachs protoptype for prevention of genetic disease. In
MCKUSICK, V.A., CLAIBORNE, R. (eds.) Medical Genetics, HP publisher, New York, 1973.
CHILDS B, GORDIS L, KABACK MM, KAZAZIAN HH JR., Tay-Sachs screening: motives for
participating and knowledge of genetics and probability. Am J Hum Genet 1976, 28, 6: 537-49.
70. MAGGIONI G., BOTTINI E., MANCINI C., GANAU R., Qualche osservazione sul costo
dell’assistenza e la profilassi delle microcitemie. In Atti del V Congresso sulle Microcitemie,
Cosenza, 4-5-6 ottobre 1973, Istituto Italiano di Medicina Sociale, Roma, 1976, pp. 522-527.
71. NUZZOLILLO, L., ref. 41.
72. KABACK M.M., Prospective control of genetic disease. Achievements and psychosocial
considerations. In Bianco (ed.) La prevenzione delle malattie microcitemiche. VI Congresso
Internazionale. Edizioni Minerva Medica, Torino, 1980, pp. 299-306. MODELL B., Ethical and
social aspects of fetal diagnosis of hemoglobinopathies: a practical view. In D. Loukoupulos (ed.)
Prenatal diagnosis of thalassemia and hemoglobinopathies, CRC Press, Inc., Boca Raton, Florida,
1988. WHO - World Health Organization, Report on the Community Control of Hereditary
Anaemias. Memorandum from a WHO Meeting. Bulletin of World Health Organization 1983, 61,
(1): 63-80. KAZAZIAN, H.H. Jr., The thalassemia syndromes: molecular basis and prenatal
diagnosis in 1990, Semin Hematol 1990 27(3):209-28. SCRIVER, C.R., BARDANIS, M.,
CARTIER, L., CLOW, C.L., LANCASTER, G.A., OSTROWSKY, J.T., β-Thalassemia disease
prevention: Genetic Medicine applied, American Journal of Human Genetics, 1984, 36: 1024-1038.
WHEATERALL D.J., The new genetics and clinical practice, Oxford University Press, Oxford.
1985. WHEATERALL D.J., Discussion. In Variation in the Human Genome, Wiley, Chichester
(Ciba Foundations Symposium 197), 1996.
73. GUALANO C., QUINTAVALLE G., Distribuzione regionale dei malati di anemia
mediterranea in Italia, oggi. Effetti degli interventi di prevenzione. In La Prevenzione dell’anemia
mediterranea in Italia, oggi. Congress Proceedings – Rome, I October 1994, Istituto Italiano di
Medicina Sociale Editore, Roma, 1995, pp. 289-296. SILVESTRONI E., BIANCO. I., GRAZIANI
B., CARBONI C., VALENTE M,, LERONE M., D'ARCA S.U., Screening of thalassaemia carriers
in intermediate school of Latium: results of four years' work. J Med Genet 1980; 17, 3: 161-4.
74. LUCCI M., SALSINI G., TOFFOLI C., RAVANI A., DOLCINI B., VENTUROLI A.,
TADDEI MASIERI M., GIOVANNI G., VULLO C., Prevalenza e prevenzione della anemia
mediterranea in Emilia Romagna. In La Prevenzione dell’anemia mediterranea in Italia, oggi.
Conference Proceedings – Roma, I October 1994, Istituto Italiano di Medicina Sociale Editore,
Roma, 1995, pp. 239-242.
75. GUALANO C., QUINTAVALLE G., ref. 73.
76. MASTROENI I., TARSITANI G., Andamento della mortalità per anemia mediterranea in
Italia. In Bianco (ed.) La prevenzione delle malattie microcitemiche. VI Congresso Internazionale,
Edizioni Minerva Medica, Torino, 1980, pp. 71-80.
77. Ib.
78. MODIANO G., ROSSI-MORI A., Distribuzione teorica e frequenza del morbo di Cooley in
Italia. In Bianco (ed.) La prevenzione delle malattie microcitemiche. VI Congresso Internazionale,
Edizioni Minerva Medica, Torino, 1980, pp. 61-70.
79. HOEDEMAEKERS R., TEN HAVE H., Geneticization: the Cyprus paradigm. Journal of
Medicine and Philosophy 1998; 23, 3: 274-87.
80. FURBETTA M., Discussion, in BIANCO I., (ed.), La prevenzione delle malattie
microcitemiche. Atti del VI Congresso Internazionale, Edizioni Minerva Medica, Torino, 1980,
p. 138.
Correspondence should be addressed to: Stefano Canali, Sezione di storia della medicina,
Dipartimento di medicina sperimentale e patologia, Viale dell’Università 34/a, 00185 Roma; email: s.canali@histmed.it.