Ernesto Ernesto BurgioBurgioComitato ScientificoComitato ScientificoISDE ItaliaISDE Italia

http://www.myfloridaeh.com/

Presentation of draft module on Waste

Ernesto BurgioISDE Italy Scientific Committee

Arguments for a correct and sustainable waste management strategy in a bio-evolutionary perspective

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27-29 01 2010

The surface of the planet is constantly traversed by streams of energy : elements switch between the four (eco)spheres(these can be depicted as interacting parts, connected by a cyclic flow of materials and energy )

If the prevailing cause of the flow of the elements are geological energy sources (geothermal energy ) irregular and aperiodic cycles result , with a prevailing geological control, as the cycle of rocks ..If the prevailing cause is instead the solar energy , with constant flow , regular and periodic cycles result, such as the water cycle and biogeochemical cycles (the cycles of the nutrients that are assimilated by living organisms)

The changes caused by humans in these balances are not irrelevant , since they go extremely faster than the geological transformations

CO2

CC66HH1212OO66

CO2

N2

CH4 NO

H2

CO2

NH3

N2

H2OH2O

H2O

H2OCO2

CO2

CO2

SO2NO2

H2O2

O2

O2

N2

N2N2

N2

N2 N2

CH4

CH4

NH3NH3

C6H12O6

SO2

N2

N2N2

O2

O2

O2

http://venus.unive.it/miche/cicli_ecosis.htm

atmosphere

biosphere lithosphere

hydrosphere

In any case are always the same atoms that run incessantly their cycles

Chemical elements that give rise to the formation of biogeochemical cyclesare about thirty, principally carbon , oxygen , sulphur , phosphorus andnitrogen .

All the geological and bio-geochemical cycles intersect and interact

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What is Pollution ?

The turnover of the elements, namely the residence-time of an element in a sector is very variable. The rule is: extremely slow in the lithosphere (geologic time), very slow in the idrosphere, slow in pedosphere (surface layer of the lithosphere involved in the development of vegetation), fast in the atmosphere , very rapid in the biosphere

The influence that the biosphere exerts - due to its high reactivity - on hydrosphere, lithosphere and atmosphereis disproportionate to its mass which is relatively small (Edward S. Deevey)

Man has greatly accelerated the movement of many materials, so that the cycles tend to be imperfect , leading to the paradoxical situation of an excess of an element on one side and simultaneously a major failing on the other .. Pollution alters the distribution of materials in two ways:- changing/accelerating the flow of elements ;- introducing some extraneous materials ( xenobiotics ) that species are unable to decompose .

(Most of the pollution occurs when certain substances, due to human activity, are either too abundant or in-sufficientin a given sector )

http://venus.unive.it/miche/cicli_ecosis.htm

atmosphere

biosphere

hydrosphere lithosphere

What is Pollution ?

Biological magnification , is the increase in concentration of a substance, such as Hg or DDT, that occurs in a food chain

Bioconcentration and bioaccumulation occur within an organism , biomagnification across trophic (food chain ) levels

Lipid , (lipophilic ) or fat soluble substances cannot be diluted, brok en down, or excreted in urine, a water-based medium , and so accumulate in fatty tissues of an organism if the organism lacks enzymes to degrade them. When eaten by another organism, fats are absorbed in the gut, carrying the substance, which then accumulates in the fats of the predator. Since at each level of the food chain there is a lot of energy lo ss, a predator must consume many prey , including all of their lipophilicsubstances.For example, though mercury is only present in small amounts in seawater, it is absorbed by algae (generally as methylmercury ). It is efficiently absorbed, but only very slowly excreted by organisms.. Bioaccumulation and biomagnificationresult in buildup in the adipose tissue of successive trophic levels: zooplankton , small nekton, larger fish etc. Anything which eats these fish also consumes the higher level of mercury the fish have accumulated..

Human activities have at least doubled the amount of mercury around the globe.

Chlorine factories , among other sources, release mercury into the atmosphere .

This mercury is deposited back onto land and water. Inorganic mercury can be converted by bacteria into the organometallic cationknown as methylmercury , MeHg+. This accumulates in fish .

What is Pollution ?

In 1958, Dr. Roy Hertz described the “steroid cycle,” a nticipating what we now call endocrine disrupter research , as follows: “. . . we have to consider that the introduction of . . . [hormones into cattle feed lots] leads to the exposure . . . of in dividuals who might otherwise not ever in their lives come in contact with such materials . . . . This is not a theoretical consideration because we . . . now have encountered two families, each with two children, who presented with simultaneously developing gynecomastia attributable to the accidental contamination of vitamin capsules by estrogens during manufacture. If such estrogens can, by stray handling, get into such pharmaceutical preparations, can they not very readily get where they are not wanted on the farm? There is one additional consideration in this regard . . . . The fecal excretion of these materials . . . will be dropped on the soil and . . . over generations there will be constant replenishme nt of the soil surface with steroidal substances of this kind. This in turn has its effect potentially on surface water-supply contamination and also potentially on the vegetable content of steroids in crops raised on su ch soil . . . . I think that we are now actually setting up a steroid cycle in our environment , and we have to give very serious consideration to its implications for our subsequent development and growth and possibly reproductive functions“

the “Steroid Cycle”What is Pollution ?

Industrial chemicals in mothers and daughters: The pollution we share and inherit

The gift our mothersnever wanted to give us

If in relation to the impact of the industrial system (and, in particular, to the excess of “combustion”) on chemical composition of atmosphere and climate , the main problem is the total quantity and the continuously increasing emissions of CO 2 and other greenhouse gases …the same attention should be paid, and even more, for w hat concerns the effects that the spread of increasingly ubiquitous (epi-geno)-toxic molecules in environment, their bio-magnification in the food chain and bio-a ccumulationin tissues (particularly maternal and fetal) is likely to have on the whole biosphere and in particular on human health ..

XXI century: a dramatic transformation of the environment and uterine microenvironment

The main problem that the myriad sources of pollution across the planet is likely to causeto our health and to future generations is indeed the load of toxic molecules many of whichare incidental products of incomplete combustion.. accumulated in our bodies : EPA(Environmental Protection Agency); US Centers for Disease Control and Prevention; EnvironmentalWorking Group (EWG) (an environmental organization specialized in environmental research)are systematically biomonitoring the body burden of toxic chemical compounds, elements, or their metabolites (Chemical Body Burden) , in biological substances since many years

Chemical Body Burden

Les origines embryo-fœtales du cancer : cancérogénèsetransplacentaireet

transgénérationnelle

Environment���� Dynamic (Epi)genome

���� Neolamarckian Paradigm

Ernesto BurgioISDE Italy Scientific Committee

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30 01 2010

Incidenza di tumori (anno/100.000) Incidenza di tumori (anno/100.000)

Poumon 80

60

40

20

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1,5

Sein

ColonEstomac

Lymphôme10

LeucLeucéémie mie lymphatilymphatiqueque

LeucLeucéémie mie lymphatiquelymphatiqueEncéphaleLymphômesNeuroblastoma-Retinoblastoma1

<1 Tessuti molli, rene (Wilms), gonadi

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ReinCerveau

In genere si afferma che itumori infantili sono una patologia rara. Bisogna però

intendersi. E’ opportunoricordare come, in terminiassoluti, di cancro si ammaliun bambino su 5-600 e cheoltre 13 mila bambini siammalano ogni anno dicancro nei soli USA ; come

nonostante i significativi miglioramenti prognosticidegli ultimi decenni il cancrorappresenti la primacausa di morte per malattiaIn età pediatrica ; comeanche in questa fasciad’età, da 40 anni a questaparte, si assista in tutto ilmondo a un incrementosignificativo e continuodella patologia tumorale

Bleyer A, O’Leary M, Barr R, Ries LA,editors. Cancer epidemiology in older adolescents and young adults 15-29 ears of age, including SEER incidence and survival: 1975-2000 . NIH Pub. No.06-5767. Bethesda (MD): NationalCancer Institute; 2006. Jemal A, SiegelR, Ward E, et al. Cancer statistics ,2008. CA Cancer J Clin 2008;58:71 – 6.

Alberto Tommasini, Laboratorio Immunologia Pediatrica, IRCCS Burlo Garofolo

Le CA est le facteur principal de décès par maladie dans l'enfance et l’on assiste à une augmentation importante et constante des tumeurs dans le monde pour ce groupe d'age

INCIDENZA DI INCIDENZA DI NEOPLASIE in INFANZIA E NEOPLASIE in INFANZIA E ADOLESCENZAADOLESCENZA IN EUROPA (anni 1970IN EUROPA (anni 1970--1999)1999)

mother

latency

Un primo report del progetto, pubblicato su Lancet nel 2004, evidenziò un incremento annuo dell’1-1,5 % per tutte le neoplasie (con aumenti più marcati per linfomi, sarcomi dei tessuti molli, tumori delle cellule germinali e del sistema nervoso).

.. come risulta chiaramente dal recente progetto ACCIS (Automated Childhood Cancer Information System ) - un ampio monitoraggio condotto da una squadra di epidemiologi IARC su 63 registri oncologici di 19 paesi europei , per un totale di oltre 130 mila tumori di tutti i tipi (113 mila pediatrici e 18 mila di età adolescenziale)

Steliarova-Foucher E, Stiller C, Kaatsch P, Berrino F, Coebergh JW, Lacour B, Parkin M. Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCISproject): an epidemiological study.Lancet. 2004 Dec 11-17;364(9451):2097-105

http://www-dep.iarc.fr/accis.htm

Miglioramenti diagnostici !?

Ucraina, Bielorussia ?!

I dati del progetto ACCIS pubblicati su Lancet furono ben presto confermati dalla successiva rassegna (la piùcompleta a tutt’oggi) dei dati emersi dallo studio, che costituisce ormai il più ampio database europeo sul cancro , pubblicata due anni dopo, in un numero monografico, dall’European Journal of Cancer: 18 articoli in tutto, che contengono l’analisi dettagliata dei dati sui tassi di incidenza e sui trends di prevalenza e sopravvivenza…

E’ sufficiente sottolineare come in 20 anni (tra il 1978 e il 1997) si sia assistito, in Europa, ad un incremento medio generale di neoplasie ad insorgenza in etàpediatrica dell’1,1% annuo (ma del 2% annuo circa nel primo anno di vità e dell’1,3% in etàadolescenziale ).

Increased risk was obtained for both cellular and cordless phones , highest in the group with >10 years latency period .

… se possibile ancora peggiori sono le notizie per i bambini italiani. I recenti dati del Rapporto AIRTUM(Associazione Italiana Registri Tumori) 2008 sui tumori infantili , dimostrano infatti come i dati di incidenza e gli andamenti temporali siano in Italia peggiori che negli altri paesi europei e negli USA (il che, sia detto per inciso, priva di qualsiasi valore l’ipotetico fattore “miglioramento diagnostico”).

Rapporto AIRTUM 2008 - Tumori infantili. Incidenza, sopravvivenza, andamenti temporali Epidemiologia & Prevenzione 2008; 32(3) Suppl 2: 1-112

Rapporto AIRTUM 2008 - Tumori infantili. Incidenza, sopravvivenza, andamenti temporali (Epidemiologia & Prevenzione 2008; 32(3) Suppl 2: 1-112)

• Periodo di osservazione 1998-2002• Incidenza (nuovi casi l’anno). Nell’area coperta dai registri

tumori i tassi d’incidenza della malattia sono i seguenti: bambini 0-14 anni: 175,4 casi per milione/annoragazzi 15-19 anni: 270,3 casi per milione/anno

• Il tasso di incidenza per tutti i tumori pediatrici in Italia èpiù alto di quello rilevato negli anni novanta negli Stati Uniti (158) e in Europa (140).Attualmente in Germania è 141, in Francia è 138

• Andamenti temporali (anni 0-14) tra il 1988 e il 2002si èosservato un aumento della frequenza del 2% annuo , passando da 146,9 casi (periodo 1988-1992)a 176,0 casi ( 1998-2002)

• L’incremento più consistente riguarda i bimbi sotto l’a nno di età (+ 3,2%), seguiti da quelli tra 10 e 14 anni (+2,4%) , mentre è simile negli altri due gruppi (+1,6% nella fascia di età1-4 anni, +1,8% tra i 5 e i 9 anni).

• I tre tumori più frequenti nei bambini sono tutti in aumento:• leucemie + 1,6% annuo; linfomi + 4,6% annuo; tumori del

sistema nervoso centrale + 2,0% annuo• Un fenomeno simile è stato osservato in diversi Paesi, • ma… in Italia il cambiamento percentuale annuo risulta

più alto che in Europa:per l’insieme di tutti i tumori (+2% vs 1,1%)per le leucemie (+1,6% vs 0,6%)per i tumori del sistema nervoso centrale (+2% vs 1,7%) per i linfomi (+4,6% vs 0,9%).

• (Negli Stati Uniti il tasso per tutti i tumori non è aumentato in modo significativo (+0,6%), l’incremento delle leucemie è dello 0,4% e i tumori del SNC sono stabili (-0,1%))

On ne peut pas expliquer tout cela par l’accumulation des lésions oxydantes comme chez les sujets plus âgés. De plus, cette augmentation touche tout particulièrement les enfants dans leur premièr e année de vie (le taux de l'incidence a augmenté de >2% dans le première année; de 1,3% pendant l'adolescence)

Prenatal origin of certain childhood leukaemias

Le processus de cancérogénèse est généralement très long…Donc, le véritable problème est l’exposition des parents ( gamètes ) aux facteurs de risque.Le processus de cancérogénèse a débuté bien avant la nai ssance de l’enfant * .

On peut aussi dire que la phase d’initiation * tumorale (1° Hit de Knudson) survient lors du développement ontogénétique du fœtus

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Trasmissione transgenerazionale 2

Alterazione memoria epigenetica-gameti

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Il n’y a que deux possibilités:1) l’exposition du fœtus à des agents physiques (X-rays ), chimiques ou biologiques ( virus)(transmis par transmission trans-placentaire ) qui puissent endamager directement le foetus 2) la transmission trans-generationelle d’une ou plusieurs lesions genètiques ou epi-génetiques

Cheryl Lyn Walker UT MD Anderson Cancer Center

Ce sont des quantités minimales de molécules (epi)génotoxiques , induisant des transformations continuelles de la chromatine , qui constituent le véritable problème. C’est un processus très lent pouvant démarrer lors des premières étapes du développement fœtal . Et, même dans les gamètes . Si les tissus du fœtus sont mal programmés au début et s’il y a un stress épigénétique progressif , les mutations génétiques et chromosomiques vont davantage se produire

À présent de nombreuses études, en différentes pays, cherchent d'évaluer la charge chimique du corps (chemical body burden) .. surtout chez les femmes, les enfants, les embryons/foetus, fournissant des résultats dramatiques. Parmi les plus connus sont les études réalisées par des chercheurs de l'Environmental Working Group, qui ont documenté la présence de centaines de substances toxiques, mutagènes et cancérigènes dans le sang, l'urine, le lait maternel, le sang de cordon: inquiétude a suscité une étude qui documenté la présence de substances (géno) toxiques et mutagènes dans tous les cordons ombilicaux testées, démontrant l'omniprésence et la précocité de l'exposition fœtale

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http://www.ewg.org/reports/generations/

ULTRAFINE PARTICLES

HEAVY METALS

EDCsdioxin-like moleculles

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Il est bien établi que l'exposition aux polluants de l'environnement inhalés ou introduites avec les aliments par la mère pendant la grossesse, peuvent perturber la programmation épigénétiquedes cellules de l'embryon et du fœtus , interférant avec la différenciation des cellules, affectant négativement la planification et le développement de divers organes et tissus, ouvrant la voie à des troubles métaboliques, aux maladies neuro-endocrines , aux maladies neuro-dégénératives et même aux maladies néoplasiques qui peuvent se produire des années/décennies plus tard, à l'âge adulte.

DOHAD

(and the Developmental Origins of Health and Diseases )

Ernesto Ernesto BurgioBurgioComitato ScientificoComitato ScientificoISDE ItaliaISDE Italia

Avian/Swine Flu: the dangerous link between Science and Hype

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Copenhagen15-16 04 2010

• The warning given out by the WHO resulted in a calamity ..in the waste of huge sums of public money .

• We were also frightened by the unnecessary idea that there were going to be ten of thousands or even hundred thousands of deaths. We also know that the priorities of many health services in many countries were distorted, money was being spent at defending against a formal flu…

• We are trying to find out the truth, what really h appened and why and which was the role of the WHO .

• In Strasbourg the evidence was not convincing and the representatives of the WHO still wanted to rely on secrecy and the privacy of the people involved…

• so we don’t really know who actually took the decisions, who decided that this was going to be defined as a phase six pandemic resulting in a great alarm all over the world...

•A pandemic cannot be whatever the WHO declares it is.

Paul Flynn (United Kingdom, Socialist), PACE rapporteur on this issue.

A pandemic cannot be whatever the WHO declares it is

Paris , 29.03.2010The second public hearing of PACE’s Committee on Social, Health and Family Affairs, on H1N1 management in Paris (20,03, 2010 ) began with these words by

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The first point is that influenza viruses are the only ones with a relatively constant and predictable behaviour . In fact flu follows a dual epidemic trend : - seasonal epidemics : when the influenza virus prevalent in the human reservoir , showing minimal mutations (genetic drift ), affects hundreds of millions of people (with significant economic and social costs) and causes a large number of deaths (in average 3-500.000/year), usually in the elderly and those with weak immune systems ; - pandemics : when, following very irregular cycles , a "new" virus coming out from the avian-flu-virus reservoir and/or recombined with human isolates in pigs ( mixing vessel ) spreads rapidly around the world, hard hitting and killing a significantly larger number of people, oftenyoung and in full health (up to 40 million deaths in a few months - 4 times more numerous than the victims of the Great War - during the Spanish Flu pandemic of 1918-19).

Timeline of emergence of Influenza A viruses in humans. The viruses isolated from pandemics in the last century are indicated by time of origin and subtype. Virus subtypes with pandemic potential are circled .

1918 H1N1 was responsible for the Spanish flu pandemic and became adapted to mammals

The Asian Flu was a pandemic outbreak of H2N2 avian-human virus influenza that originated in China in 1957H3N2 evolved from H2N2 by antigenic shift and caused the Hong Kong Flu pandemicis

1968-69. It is currently endemic in both human (since 1968) and pig populations (since 1997-8).

In 1976, a novel swine influenza A (H1N1 ) caused the swine hoaxin US: 40 millions vaccinated � 500 G.Barré syndrome (35 deaths ?). The 1977–1978 Russian flu was caused by a lab strain ..

A/USSR/90/77 (H1N1).?!!

In the last 13 years many H5.. H7.. H9 pantropic avian viruses emerged from avian reservoirs and provoked some clusters of human flu which cause concern …

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On one hundred people in a year seven will have a FLU .. One is caused by an influenza A or B virus . This is an exaggeration as well, because many of these BLUE GUYS are infected by more than one bug..

Paris , 29.03.2010

On average, perhaps 1 adult out of a 100 vaccinated will get influenza symptoms compared to 2 out of 1 00 in the unvaccinated group . To put it another way we need to vaccinate 100 he althy adults to prevent one set of symptoms. However, our Cochrane review found no credible evidence that there is an effect against complications such as pneumonia or death

.. Vaccines and antivirals have a weak or non-existent scientific evidence base..

TO Jefferson, D Rivetti, C Di Pietrantonj, A Rivetti, V Demicheli. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD001269. DOI: 10.1002/14651858.CD001269.pub3.

Paris , 29.03.2010

In children under 2 years inactivated vaccines had the same field efficacy as placebo , and in healthy people under 65 vaccination did not affect hospital stay, time off work, or death from influenza and it s complications. Reviews found no evidence of an effect in patients with asthma or cystic fibrosis..

.. In children under 2 years inactivated vaccines had the same field efficacy as placebo..

Inevitably the first question that comes to mind is: can we draw the line between the necessary and legitimate experiments aimed at improving the effectiveness of medicines (and especially vaccines ) and mass experimentation in situations where the need of an early intervention may appear a global priority ?

??!!??

the first question .. can we draw the line between the necessary and legitimate experiments .. and mass experimentation in such situations ?

The second question, closely related to the first one, is: is it correct to affect the development of the immune system in hundreds of millions people (particularly in children !) with new (experimental) adjuvants acting (with mechanisms still unknown ) by stimulating both the natural (TLRs) and the adap tive immunity ?

This is a paper publishedby NovartisExperts !

Most of the concerns raised almost 30 years ago still remain valid today, although perhaps we now know a little more about how the adjuvants work . Even back in 1980, it was highlighted that there were concerns that potent immune stimulators could potentially trigger autoimmune diseases ,

a great problem are: chicken and turkey breedings .. swine farming … and wet markets

The third question , which follows the first two, is : are we truly convinced that the best way - the most effective and, at the same time, surer - to tackle the flu-problem in its dual form (seasonal epidemic / pandemic) is mass-active immunoprophylaxis ?Or there are better possibilities for a true primary prevention , right there (large pig farms, wet marketsetc...) where many different strains can easily exc hange genetic material , producing new flu-viruses?

.. we are living in a pandemic era that began around 19 18… At that time, a presumably “new virus"

..probably derived from an unidentified avian-like p recursor virus, became adapted to mammals .. causing an explosive and historic pandemic, during which humans also transmitted the virus to pigs, in which it remains in circulation . Ever since 1918, this tenacious virus has survived .. in both humans and pigs ..The 2009 H1N1 pandemic virus represents yet another gen etic product in the still-growing family tree of this remarkable 1918 virus. To understand what has been happening since 1918, it is helpful to think of influenza viruses not as distinct entities but as eight-member "gene teams" that work together

This is perhaps the mostimportant paper on swine-flu published last year. The author was JeffreyTaubenberger , one of the most famous experts in the field, having sequenced the H1N1 virus of the 1918 Spanish Flu

In his paper Taubenberger showed that the theory of 3(4) pandemics (due to antigenic shift) in the twentieth century is an oversimplification . … sometimes a simple drift (last time in 1997-99) caused a large number of deaths

Except for the classical swine H1N1 virus , most of these contemporary H1 and H3 strains are triple reassorta nt viruses , containing genes of avian, human , and swine flu-virus origin.

From when it was first isolated in 1930 until 1998, the classical H1N1 (cH1N1) subtype of SIV was essentially the only SIV lineage circulating in the US swine population . Genetically and antigenically, the cH1N1 SIV and the human influenza virus implicated in the 191 8 Spanish Flu pandemic are similar .

Beginning in 1998, however, clinical disease caused by H3N2 subtypes was recognized in a few states and soon spread throughout the entire country. Described as reassortant viruses, the original H3N2 strain had three genes from a human H 3N2 influenza virus that circulated in the human population during 1995, as well as five genes from the cH1N1 SIV . The initial outbreak of influenza attributed to H3N2 occurred during August of 1998 in a North Carolina pig farm

classical H1N1

cH1N1 SIV

.. it is significant that one of the North American H1N2 ** ‘triple reassortants’closest to S-OIV is probably used in commercial multivalent pig vaccines in North America

**

In this diagram the genetic evolutionof the H1N1 virus iswell represented. We can see(on the left) the 1918/H1N1 whichis the common ancestor of all the human (and swine) flu-viruses of the lastcentury.. Then we can see how, through some mutations, the triple reassortantswere created(1998-2009)..

The real question is

the origin of the new genes ...

What is really striking in the genetic sequences published by Lancet in Aug 2009 is the reappearance of the Neuramidase gene after many years (in these cases the main possibilities are that these genescome from a virus kept in a laboratory , or employed in some animal vaccines

Experiments are underway to determine whethercurrently available vaccines may be able to providepigs with a certain immunity to stop a potentialspread of the virus

In fact the frequent use of vaccines in swinefarming is striking . And noone seems to take intoaccount the possible dangers of this practice

…the similarity of gene segments of A/Swine/Guangdong/z5/2003 was closer to Moscow/99-like human H3N2 virus than Europe swine H3N2 viruses during 1999–2002. These results suggest that A/Swine/Guangdong/z5/2003 may be porcine in origin, possibly being driven by human immune pressure indu ced by either natural H3N2 virus infection or use of A/Moscow/10/99 (H3N2)-bas ed human influenza vaccine .

And I am not alone in supposing that using human flu vaccines in animals

is a possible cause of immune pressure-driven cross-sp ecies transmission

Given the evidence that pigs can supportthe reassortment of influenza viruses fromhumans and other species , it is prudent that we enhance surveillance foratypical influenza viruses in pigs as part of overall pandemic preparedness efforts ."

(J.Y. Shin, M.S. Song, E.H. Lee, Y.M. Lee, S.Y. Kim, H.K. Kim, J.K. Choi, C.J. Kim, R.J.Webby, Y.K. Choi. 20062006. Isolation and characterization of novel H3N1 swineinfluenza viruses from pigs withrespiratory diseases in Korea. Journal of Clinical Microbiology, 44. 11: 3923-392

The first isolation and characterization of the novel subtype H3N1 in Europe was described.

The complete HA gene presented the highest identity to three Ita lian H3N2 SIVs isolated in 2001 and 2004, whereas the NA gene was instead closely relat ed to three Italian H1N1 SIVs isolated in 2004 . The deduced aa sequence of the HA gene showed the aa residues (L226 and S228) responsible for the rece ptor specificity typical of swine and human influenza viruses… This suggested that the novel SIV was a reassortant between the H3N2 and H1N1 SIVs circulatin g in Italy.

A risk we run is that crying "wolf.. wolf " if the wolf really comes people will not believe us .. But perhaps the greatest risk we must face comes from Someone’s project to use such alarms for a large mass experimentation

But it is important that we move towards strengthen ing the supervision and strict hygiene regulations upstream : in Asian wet markets , where birds, mammals and people live in unacceptable degree of promiscuity, in large avian flocks (where for several years the avian epidemics have multiplied), in industrial pig farms , because, in fact, it is in these places that emerge the new strains, potentially dangerous to humans…probably due to the artificial selection pressure generated by the use of experimental drugs and vaccines (a very dangerous habit to be avoided, as preventiv e use of antibiotics).. as some recent studies show that the "new sequences" of the S-OIV/2009 were not entirely new… one of the possible hypotheses is that these come from weakened viruses employed in veteri nary immuno-prophylaxis …

We should neither even forget that most reports of emerging-disease events come from developed countries .. nor that many EID are zoonoses…

I geni di antibiotico-resistenza: nuovi “inquinanti ambientali”?

"... the mounting use of antibiotics, not only in people, bu t also in animals and in agriculture , has delivered a selection unprecedented in the history of evolution ."

Levy, 1997

Ernesto Ernesto BurgioBurgioComitato ScientificoComitato ScientificoISDE ItaliaISDE Italia

Workshop NazionaleFARMACI, SALUTE E AMBIENTE

1° Luglio 2010 Firenze, via Nicola Porpora 22 (FI), Direzione generale di ARPAT

4Firenze1 07 2010

transition from developing to developed status during the twentieth century

Figura 6. Sviluppo ed efficacia della chemioterapia antimicrobica negli scorsi sessant’anni. da: Periti P. e Noselli A. Farmaci e Terapia 1996; 13:3-28

Vaccinazione obbligatoria

Figura 7. Difterite 1 : morbosità in Italia. da: Le Vaccinazioni in Italia. Collana Fondazione Smith-Kline. Milano CIS editore, 19961

ab

a) Introduzione vaccino Salk

b) Diffusione vaccino Sabin

Figura 8. Poliomelite : morbosità in Italia. da: Le Vaccinazioni in Italia. Collana Fondazione Smith-Kline. Milano CIS editore, 1996

N.B. L’insuccesso della prima vaccinazione (a) è stato attribuito a diffusione parziale, e a insufficiente efficienza della “catena del freddo)

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Figura 4. Morbosità, mortalità

(cifre proporzionali a 1.000.000 di

abitanti) e letalità per scarlattina , in

Italia. Dal 1888 al 1949.

Penicillina G

Antibiotic Resistance: An Ecological Perspective

Tremendous quantities of antibiotics are produced and released into the environment *90 – 180 million kg/year of antibiotics are used (enough for 25 BILLION full treatment courses ~ 4 per human/yr!)About 10 X more antibiotics are used in agriculture than to treat people. (Levy 1997 estimated 30 X more in animals than in people ).

“There are two major effects of an antibiotic: therapeutically, it treats the invading infectious organism, but it also eliminates other, or non-disease producing, bacteria in its wake . The latter do, in fact, contribute to the diversity of the ecosystem and the natural balance between susceptible and resistant strains.…The consequence of antibiotic use is, therefore, the di sruption of the natural microbial ecology * . This alteration may be revealed in the emergence of types of bacteria which are very different from those previo usly found there , or drug resistant variants of the same ones that were already present.”Levy, 1997

http://www2.nau.edu/~bah/BIO471/Lecture_6.ppt - 67k

S. aureus

Penicillin

[1950s]

Penicillin-resistant

S. aureus

EvolutionEvolution of Drug Resistance in S. aureus

� Link to: CDC Facts about VISA� Link to: CDC Facts about VRE

Methicillin

[1970s]

Methicillin-resistant

S. aureus (MRSA)

Vancomycin-resistant

enterococci (VRE)

Vancomycin

[1990s]

[1997]

Vancomycin

intermediate-resistantS. aureus(VISA)

[ 2002 ]

Vancomycin-

resistantS. aureus

� Link to: MMWR on VRSA

… specific antibiotics (namely tobramycin, tetracycline, and norfloxacin) at subinhibitory concentrations trigger expression of determinants influencing the virulence of the major opportunisticbacterial pathogen Pseudomonas aeruginosa. All three antibioticsinduce biofilm formation ; tobramycin increases bacterial motility , and tetracycline triggers expression of P. aeruginosa type III secretionsystem and consequently bacterial cytotoxicity.

Besides their relevance in the infection process, those determinants are relevant for the ecological behavior of this bacterial sp ecies in natural, nonclinical environments, either by favoring colonization of surfaces ( biofilm , motility ) or for fighting against eukaryoticpredators ( cytotoxicity ).

Our results support the notion that antibiotics are not only bacterialweapons for fighting competitors but also signalingmolecules that may regulate the homeostasis of microbialcommunities .

At low concentrations, they can even be beneficial for th e behavior of susceptible bacteria in natural environment s.

This is a complete change on our vision on the ecologic alfunction of antibiotics

Linares JF, Gustafsson I, Baquero F, Martinez JL. Antibiotics as intermicrobial signaling agents instea d of weapons . Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19484-9.

E’ stato anche dimostrato da tempo che tali molecoletali molecole --segnale sono segnale sono ubiquitariamenteubiquitariamente diffuse in tutti gli diffuse in tutti gli ecosistemiecosistemi , essendo prodotte e trasmesse orizzontalmente trasmesse orizzontalmente tra microrganismi anche molto distanti tra microrganismi anche molto distanti tra loro sul piano genetico e tra loro sul piano genetico e filogeneticofilogenetico e che anche la gran parte delle resistenze si producono e trasmettono in questo modo .

Martínez JL.Antibiotics and antibiotic resistance genes in natural environments Science. 2008 Jul 18;321(5887):365-7.

Alonso A, Sánchez P, Martínez JL. Environmental selection of antibiotic resistance genes. Environ Microbiol. 2001 Jan;3(1):1-9

Martínez JL, Baquero F, Andersson DI. Predicting antibiotic resistance Nat Rev Microbiol. 2007 Dec;5(12):958-65

Lo studio di questa complessa rete di segnali e interazioni molecolari dovrebbe portare ad una rappresentazione finalmente eco-sistemica in cui gli aspetti di comunicazione e cooperazione tra organismi superiori e comunitàmicrobiche siano meglio riconosciuti e valutati rispetto a quelli competitivi

Davies J Everything depends on everything else . Clin Microbiol Infect. 2009 Jan;15 Suppl 1:1-4.

Xu J and Gordon J I 2004 Honor thy symbionts ; Proc. Natl. Acad. Sci. USA 100 10452–10459

The large majority of antibiotics currently used for treatinginfections and the antibiotic resistance genes acquired by humanpathogens each have an environmental origin

Changes in natural ecosystems, including the release of large amounts of antimicrobials , might alter the population dynamics of microorganisms , including selection of resistance ,

Un ambito nel quale una simile simile capacitcapacit àà dei microrganismi dei microrganismi di di acquisire rapidamente acquisire rapidamente ““ armi genetichearmi genetiche ”” assume un’enorme importanza èquello dell’acquisizione di acquisizione di antibioticoantibiotico --resistenza.resistenza.

Many of the known antibiotic resistance genes are found on transposons, integrons or plasmids , which can be mobilized and transferred to other bacteria of the same or different species .

There is evidence of the transfer of resistance elements to known human commensal bacteria and pathogens and gene transfer in the human intestinal microbiome is ext ensiveWhat are the sources and reservoirs of these transferable genes?

A full understanding of the pressures and circumstances that lead to the evolutionand dissemination of antibiotic resistance genes in pathogens is impossible without adetailed examination of the origin and role of resistan ce genes in natural environments

Fig 10.28 Atlas, 1997

AntibioticsAntibiotics are probably driving the evolution and spread ** of resistance p lasmidsdriving the evolution and spread ** of resistance p lasmids

http://www2.nau.edu/~bah/BIO471/Lecture_6.ppt - 67k

Baquero F, Blázquez J Evolution of antibiotic resistanceTrends in Ecology & Evolution(1997)12, 12, 482-487

Microbial resistance to antibiotics currently spans all known classes of natural and synthetic compounds

Soil-dwelling bacteria produce and encounter a myriad of antibiotics, evolving corresponding sensing andevading strategies . They are a reservoir of resistance determinants that can be mobilized into the microbial community.

We isolated a morphologically diverse collection of spore -forming bacteria from soil.. originating fromdiverse locations (urban, agricultural, and forest). Strains that resembled actinomycetes-Streptomyces, whosespecies synthesize over half of all known antibiotics… We constructed a library of 480 strains that wassubsequently screened against 21 antibiotics..

The level and diversityof resistance uncoveredin this work is onlypartially reflective of the true extent of the environmentalresistome, becausethis study was restrictedexclusively to culturablespore-forming bacteria ,

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1

Without exception, every strain in thelibrary was found to be multi-drug resistantto seven or eight antibiotics on average, withtwo strains being resistant to 15 of 21 drugs

80% of the resistant strains assayedinactivated daptomycin after 48 hours..

Extensive daptomycin resistance was notanticipated. Recently approved by the Food and Drug Administration (FDA), daptomycin ishighly active against Gram-positive bacteria , including multi-drug–resistant pathogens…

The frequency of high-level resistanceseen in the study to antibiotics that havefor decades served as gold-standard treatments , as well as those only recentlyapproved for human use , is remarkable.

No class of antibiotic was spared with respect tobacterial target or natural or synthetic origin .

Although this study does not provide evidence forthe direct transfer of resistance elements fromthe soil resistome to pathogenic bacteria , itidentifies a previously underappreciated density and concentration of environmental antibioticresistance ….

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Antibiotic resistance is now a linked global proble mAntibiotic resistance is now a linked global proble m. Dispersion of successful clones of Dispersion of successful clones of multidrugmultidrug resistant (MDR) bacteria resistant (MDR) bacteria is commonis common, often via the movement of people . Local evolution of MDR bacteria is also important under the under the pressure of excessive antibiotic use, with horizont al gene transpressure of excessive antibiotic use, with horizont al gene trans ferfer providing the means by which genes such as genes such as blaCTXblaCTX --M spread amongst different bacterial species and st rainsM spread amongst different bacterial species and st rains

Ernesto BurgioISDE Italy Scientific Committee

DOHAD X rays

Metals

Viruses

CEM

Xenobiotics

EDCs

Environment ���� Dynamic (Epi)-Genome���� Neolamarckian Paradigm

2

31

1

23

4

Ambiente e malattie rare: il paradigma epigenetico

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6

3

Evo – Devo ? Devo – Evo !

4

5

5 Firenze 20 09 2010Roma 24 09 2010

TCDD

Viruses

HERVs

CEM

3

2

1

SYNERGISM ?!

“FLUID EPI-GENOME”

4

9

Dovremmo rappresentare l’”ambiente “ come un flussocontinuo di informazioni semplici - i fotoni : singoli pacchetti di E = M = Informazione - o complesse(molecole organiche … virus … etc..) in grado di interagire con le cellule (recettori membranari � proteine di trasduzione � (epi)-genoma…)…

Non selfNon self

““Ambiente””

Self

(Epi)-genoma

Genoma

virus HERVs

Antigeni

MHC

SistemiNeuro-endocrino

ImmunocompetenteFall-Out Chimico

Agenti Fisici

Agenti Biologici

Danger Signals

Onco-géni

C-oncV-onc((Retro-viruses)

Biosfera

Genosfera

FetalProgramming

I processi filo-genetici

durano milioni di anni

DrammaticaTrasformazioneAmbientalee Climatica

Evo

Co-evoluzione

Adattamento

IXX-XX SECOLO

>100mila molecole “nuove”non portato di una di co-evoluzione

1

2

3

Challenge “naturale””

(Retro)Trasposons)

Tolleranza

Lo sviluppo onto-geneticodura 9 mesi � una vita Devo

Milioni di anni

Everyday levels matterEveryday levels matter

At truly low levels At truly low levels ……it interferes with it interferes with gene activationgene activation

At high levels… arsenic kills people

At moderately low levels…it causes a range of diseases

KaltreiderKaltreider et alet al. 2002. 2002

Mismatch Repair EnzymesTrascription Factors

Hormones

Correct organizationof chromatin

Gene- and tissue-specific epigenetic patterns

“Silencing “ mobile sequences

Genomicimprinting

X chromosome inactivation

Controlling active and inactive states of embryonic and somatic cells

B

A

1 2

3

4

5

6

Epigenetic perturbations early in life

Epigenetics and human disease

Diethylstilbestrol

Organismo(adulto)

SistemiPsico -Neuro -

Endocrino -

Immuno..

Ontogenesi

Cause Prossime Cause Remote

105mila molecole di sintesi

Microrganismi

Virus

Solventi

Metalli Pesanti

Pesticidi

Filogenesi

Genoma (specie specifico) *

Endocrine Disruptors

AMBIENTE

EMF (CEM)

Microambiente Uterino

PCBsDiossine

POPs

Quadro generalePaleozoico“Esplosione Cambriana” (570 milioni di anni fa): si originano tutti i phyla di animali oggi esistenti (piani di sviluppo)Regno Animali (pluricellulari)

Philum CordatiSubphilum Vertebrati

Tra Mesozoico e Cenozoico (tra 140-65 milioni di an ni fa)Classe Mammiferi

Ordine Primati 6-8 milioni di anni Famiglia Ominidi

Genere Homo Specie Homo Sapiens 100. 000 anni

(DNA codificante *95% stabile)

Milioni di anni di lenta co-evoluzione molecolare…

Epi-GENOMA Dinamico e Adattativo *

Prima crisi dis-adattativaRivoluzione agricola : trasformazione urbanistica e sociale zootecnia trasformazione ecosistemi trasformazione dieta - celiachiatrasformazione microbiotatrasformazione micro-biocenosi � e patocenosiENDEMIE/EPIDEMIE (circa 10.000 anni: ERA DELLE MALATTIE INFETTIVE )

Seconda crisi dis-adattativaI Rivoluzione industriale II Rivoluzione industriale (chimica++)In specie a partire dal II dopoguerra: plastiche, a ntibiotici, pesticidi, POPsEsposizione progressiva… bioaccumulo-biomagnificazio ne..

MALATTIE CRONICO-DEGENERATIVE (da Cause Endogene: C AUSE REMOTE) *

Stress epi-genetico

collettivo *

Flogosi subacuta-cronica

Cancer

morfogeni

differenziazione cellulare

Cause Prossime

http://www.ilsi.org/NR/rdonlyres/15CC21E6-FA33-4DB5-9936-B15A52D5B4C4/0/03Gilman.pdf

Incremento patologie cronico-degenerative[immunomediate, neuro-degenerative, endocrine, neoplastiche, cardiocircolatorie]

L’incremento delle malattie cronico-degenerative: la difficile valutazione delle possibili cause ambientali

The gift our mothersnever wanted to give us

http://www.ewg.org/reports/generations/CHEMICAL FALL OUT

ULTRAFINE PARTICLESHEAVY METALSENDOCRINE DISRUPTORSdioxin-like moleculles1

2 3

Congresso Nazionale SIP Roma 22 10 20106

Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA

Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA

A few industrial chemicals (eg, lead, methylmercury, polychlorinated biphenyls [PCB s], arsenic , and toluene ) are recognised causes of neurodevelopmental disorders and subclinical brain dysfunction.

Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than those affecting adult brain function

Another 200 chemicals are known to cause clinical n eurotoxic effects in adults…The toxic effects of such chemicals in the developing human brain are not known and they are not regulated to protect children

A Silent PandemicIndustrial Chemicals Are Impairing

The Brain Development of Children Worldwide

1

2

3

1

2

3

Antennas on Buildings(Kitchen, 2001)

shadowregion

1 50 100 200 300 m

Distance (m)

Power Density (micro/m2)0.28 0.06 0.04 0.16 0.07 µW/m

Fire Station101

reflection

Electrosmog

Specific DNA sequences on the promoter of the HSP70 stress gene are responsive to EMF…

Hsf-1

Synthesis of this stress protein is initiated in a region of the promoter where a transcription factor known as heat shock factor 1 (HSF-1) binds to a heat shock e lement (HSE). The EMF sensitive region on HSP70 promoter is upstream from the thermal domain of the promoter an d is not sensitive to increased temperature . The binding of HSF-1 to HSE occurs at −192 in the HSP70 promoter relative to the transcription initiation site. The EMF domain contains three nCTCTn myc-binding sites −230, −166 and −160 relative to the transcription initiation site and upstream of the binding sites for the heat shock (nGAAn) and serum responsive elements….

The electromagnetic response elements (EMREs) have also been identified on the c- myc promoter and are also responsive to EMF

HSP70 stress gene

I.Fairlie Commentary: childhood cancer near nuclear power sta tions . Environmental Health 2009;8:43

• Nel 2008 lo studio KiKK (Kinderkrebs in der Umgebung von Kernkraftwerken = tumori infantili nelle vicinanze di impianti nucleari) ha rilevato un incremento di 1.6 volte dei tumori solidi e di 2.2 volte delle leucem ie tra i bambini di età <5 anni residenti entro 5 km da tutti gli impianti di energ ia nucleare in Germania.

• Lo studio ha suscitato un ampio dibattito in German ia ma ha ricevuto scarsa attenzione altrove . Eppure si è trattato di uno studio caso-controllo importante , per una serie di motivi.

• Primo: ha esaminato tutti i tumori insorti attorno a tutti i 16 reattor i nucleari tedeschi tra il 1980 e il 2003 .

• Secondo: è stato uno studio indipendente, commissionato dall’Agenzia per la radioprotezione del Governo Federale Tedesco .

• Terzo: la validità dei suoi risultati è stata ammessa dallo stesso Governo…… che ha però concluso che lo studio non è stato in g rado di fornire delle plausibili ragioni biologiche, in quanto le correnti conoscenze di epidemiologia e radiobiologia non consentono di concludere che le radiazioni ionizzanti emesse delle centrali possano essere la causa.

1

2

Ernesto Ernesto BurgioBurgioComitato ScientificoComitato ScientificoISDE ItaliaISDE Italia

Fetal programming and EDCs

7 Congresso Nazionale AME Napoli 5-7 11 2010

….NON si tratta di una tematica di esclusiva pertinenza endocrinologica …e/opediatrica

Organismo umano: clone cellulare derivato da un’unica cellula totipotente(zigote) e costituito da miliardi di cellule con unico DNA e differente (epi)genoma

Parole chiaveEDCsDOHADFetal ProgrammingFluid (Epi-Genome )

Finestre di Esposizione

Cellule totipotenti…multipotenti…

Differenziazionecellulare

PlasticitàpotenzialitàMASSIMA

Gli interferenti endocrini sono sostanze mimetiche o comunque in grado di interferire sul cell signaling intercellulare e intracellulare a vario livello: comunicazione intercellulare (discorso analogo potrebbe esser fatto per gli antibiotici tra gli organismi monocellulari), sui recettori membranari e nucleari, sulle pathways di trasduzione dei segnali dalla membrana al nucleo, sui meccanismi di trascrizione, traduzione etc. Gli effetti più significativi sono connessi alla possibile loro azione su cellule/tessuti di organismi in via di sviluppo, con particolare rilievo per specifiche fasi di sviluppo di organi e tessuti (finestre di esposizione ). Il problema fondamentale (in ambito biomedico) connesso alla diffusione in ambiente (catene alimentari !) di molecole xenobiotiche, metalli pesanti ecc.. in grado di agire da interferenti endocrini (perturbatori informatici) può essere riassunto in una sigla: DOHAD

12

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Insulino-resistanceDiabetes

Cardiovascular Diseases

the XX Century Epidemic Revolution

Barker Hypothesis (1989)

(1989)

ab

c

We may even hypothesize that a lot of diseases characterizing what we may call the XX Century Epidemic Revolution [the epidemic change we are witnessing all over the world, and especially in the most developed countries, concerning a switch from a prevalence of acute exogenous(infectious and parasitic) to a prevalence of chronic endogenous (immuno-mediate, neurodegenerative, neuro-endocrine, cardiovascular and neoplastic) diseases, - atopy/asthma and autoimmune disorders (diabetes I, celiac disease etc); obesity, metabolic syndrome, diabetes II; atherosclerosis (stroke, infarct etc); Alzheimer Disease, Parkinson Disease; Cancer] is a late result, in adults, of a developmental process gone awry, deeply rooted in t he first stages of embryo-fetal development

• ENVIRONMENT HEALTH• Genome and Epi-genome• The Epidemic Revolution of XXth Century• 3 PARADIGMS

Barker HypothesisHygiene HypothesisSystemic-chronic (low grade) Inflammation

• Back to the NEO-LAMARCKIAN PARADIGM ENVIRONMENT � Epigenetic Changes

���� Fetal ProgrammingFluid (Epi)genome

1

2

3

Exposure during a critical period in development may influence later metabolic functions in adult life

+

philo-genetic > ontogenetic ?

Environmental exposures have been found to promote several transgenerationaldisease states or phenotypes

The reproducibility and frequency of these disease phenotypes suggests they are likely epigenetic rather than due to DNA sequence mutations.

The exposure of a gestating mother exposes the F0 generation mother, the F1 generation embryo and the germ-line of the F2 generation.

The F3 generation would be the first unequivocal transgenerational generation not exposed .

Research has demonstrated that 90% of all male progenyfor four generations (F1–F4) developed these diseas e statesafter the direct exposure of the F0 gestating rat This transgenerational phenotype was only transmitted thr ough the male germ-line (sperm ) and was not passed through the female germ-line (oocyte).

These animals had the following disease state frequencies; 20% tumor development ,50% prostate disease , 40% kidney disease, 30% immune abnormalities, and 30% severe infertilit y in males from F1 to F4 generations

From Genetics to EpigenomicsThe Times They Are A-Changin'

Ernesto BurgioISDE Italy

Scientific Committee

8

EHP High Level Expert MeetingBruxelles 8-10 11 2010

On the contrary, in the almost 25 years of its history, HGP produced a great progress in understanding the genome and its way of “workingand changing” in response to information and stimuli coming from the environment, enabling us to understand:

1) that cells and organisms function as (eco)-systems(A "systemic“ representation of lifeis becoming one of the basic ideas in modern biology….)

http://news.sciencemag.org/sciencenow/2009/04/21-03.html

….the whole Genome is a Complex and highly dynamic molecular Networkof interacting Genes and non-codifying sequences .. and proteins

To summarize

It is not true that the Human Genome Project (HGP) was a failure …… We would rather say that HGP has provided us with great scientific advancements …even if these findings are not the ones expected by those who had invested heavily in it (even in economic terms) hoping to quickly find new diagnostic and therapeutic tools in medicine

1b … that all permanent changes in our phenotype (both physio logical and pathological) are the product of complex interactio ns between environment, epigenome and genome ;

1c … that trans-generational changes in epigenetic setting of tissues and organs could (help us to) explain the dramatic increase in chronic diseases, in all countries characterized by industrial develo pment and western lifestyles... A transformation we may call "Epidemic Revolution of the twentieth century "

An "Epidemic Revolution of the twentieth century "consisting of a significant increase in endocrine and metabolic disorders(obesity, metabolic syndrome, diabetes II); neurodegenerative diseasesand disorders of neuropsychological development (ADHD, autism, Alzheimer and Parkinson diseases); cardiovascular (atherosclerosis, hypertension, vasculitides); immune-mediated diseases (allergies, autoimmune diseases); cancer ..

• The key model in this context is certainly DOHAD(Developmental Origins of Health and Diseases).

• A pathogenic model , initially applied to some specific areas (cardiovascular, endocrine and metabolic diseases)… we should use as a sort of universal pathogenic paradigm… recognizing in many adult diseases the late product of an altered tissue programming in utero (fetalprogramming ), responsive/adaptive to environmental/micro-environmental conditions/information

• perceived as potentially dangerous for the single organism or simply different from those for which it was genetically programmed

The problem is how to evaluate the consequences of these epigenet ic ���� genomic changes on populations chronically (daily) exposed to heavy metals and other epigeno-toxic pollutants ??!!

We also know that if we expose primates (and other mammals) in the very first stages of their development to some xeno-biotics(endocrine disruptors etc) or to heavy metals (mercury, lead, cadmium) we induce fetal programming (modifying the epigenetic setting of their endocrine and immunological tissues) conditioning the whole life of their cells and tissues and opening the way to many diseases (breast cancer, Alzheimer disease..)

• Finally it is important to emphasize that all the current - epidemiological and toxicological - methods of assessing the risk associated with environmental pollution are proving to be inadequate..

• to evaluate the possible effects of the dramatic molecular transformation produced by man in a few decades

Our common ways of evaluating the risks for our health and the risks for the new generations' health , directly connected to environmental pollution, are absolutely insufficient . As a matter of fact “classic” epidemiological and toxicological studies are not the right way to evaluate the threat posed by “global” environmental pollution to our health, to new generations' health , to ecosystems . ..Epidemiologists generally evaluate the

diseases' burden directly connected with environmental pollution by comparing

two populations - the one more directly exposed to a known source of pollution

(a factory/industrial implant or incinerator..or a highway with high traffic rate)

the other supposed to be much less exposed.. Systematically

forgetting that nowadays we are all exposed (through the nutritional chains and through direct transgenerational transmission of pollutants from our mothers )

to a constantly growing burden of xenobiotics (more than 100.000 synthetic molecules) that cannot be recognized by our cellular and nuclear receptors and that may interact in a wrong way with our biochemical pathways and sometimes even with the genetic expression of our cells and tissues.

• Gli studi tossicologi possono dimostrare gli effetti patogeni/cancerogeni a breve termine su animali (che spesso hanno sistemi di trasformazione enzimatica, pathways metaboliche e di trasduzione dei messaggi bio-chimici e di programmazione ed espressione genetica differenti dai nostri) ma non possono nédimostrare, né escludere che gli stessi effetti si verifichino nell’uomo, tanto meno possono documentare gli effetti indiretti e a lungo termine (pro-flogogeni e pro-cancerogeni, transplacentari e transgenerazionali )

Toxicological studies can demonstrate the effects of pathogens/carcinogens in the short-term on guinea-pigs (which often have processing enzymes, metabolic ..cell-signaling and gene expression pathways quite different from ours), but can neither prove or exclude that such effects occur in humans.. and even less document the indirect and long-term effects (pro-inflammatory and pro-carcinogen, transplacental and transgenerational)

• Non sarebbe più utile e corretto, per valutare la bio-so stenibilità , delle fonti di inquinamento e in particolare di impianti come gli inceneritori di RSU…(oltretutto enormemente dispendiosi sul piano economico ed energetico e facilmente sostituibili con una corretta filiera di processamento, incentrata su raccolta differenziata spinta, recupero e trasformazione dei materiali cartacei, plastici, metallici e dell’umido per il compostaggio)

• … basarsi sulla quantità complessiva di agenti tossici - (epi)genotos sici, mutageni e cancerogeni , bio-accumulabili da parte di singoli organismi, bio-magnificabili negli ecosistemi - prodotti e immessi in ambiente (rilevabili mediante l’utilizzo di semplici centraline e di bio-marcatori di esposizione e bioaccumulo: presenza di metalli pesanti cancerogeni in licheni epifiti)

• e sul suaccennato concetto di carico chimico globale ?

SOLUZIONE: Calcolo Emissioni e Carico Chimico Globale

Wouldn’t it be more useful and correct, to assess the bio-sustainability , of various sources of pollution (and in particular of incinerators which are the most dangerous, costly, and unsustainable method of treating waste, and could easily be replaced with a proper chain of process, focusing on waste collection drive , recovery and processing of paper materials, plastic, metal .. and moisture for composting ... .. on the total quantity of toxic agents - (epi) genotoxic, mutagenic and carcinogenic, bio-accumulative by individual organisms, bio-magnified in the ecosystem - produced and released into the environment (detectable by using simple control units and bio -markers of exposure and bioaccumulation: the presence of carcinogenic heavy metals in epiphytic lichens), and on the concept of chemical burden ?

• A global/molecular transformationwhich could interfere with the epigenetic setting of organs and tissues and,

• in the long run, even with the genetic setting of our and other species :

• an immense problem that does not seem addressed to date with sufficient attention.

HSPsActivation

HSPs/petidesDanger Theory(Auto)Immunity

Autoinflammation

ROS

Epidemic Revolution of the twentieth

century

Environment

mRNAs

fluid (epi)genomeNeo-LamarckianParadigm

developmental plasticity

Health / DiseasesEnvironmental Pollution �

Medico Sentinella

Agenti fisici (!)

Fonti di inquinamentoPuntualiDiffuse

Agenti biologici (!)

Agenti chimici (!)

cocktail

sinergismo

piccole dosi quotidiane(Epi)genoma reattivo

(Epi)-genetic-Instability

Tempo di latenza protratto

(decenni � generazioni)

Esposizione collettiva ++

embrione/feto-bambiniDOHAD

marcature epi-genetiche

Trasmissione e amplificazione transgenerazionale del danno

Cause Remote

Cause Prossime

Milioni di anni di lenta co-evoluzione molecolare…

Limiti degli attuali modelli di patogenesi

Genoma (specie specifico) stabile * Stress epi-genetico collettivo *

gameti

Rivoluzione epidemica XX Secolo

15

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God does not play dice È la celebre affermazione che suggella l'acceso dibattito tra Einsteine i sostenitori di una certa interpretazione della fisica quantistica…

God is subtle but not malicious

I believe in Spinoza's God who reveals himself in the orderly harmony of what exists

“A clever man solves a problem, a wise man avoids it”

‘‘We can’t solve problems by using the same kind of thinking we used when we created them’’