Nanotoxicology and Particle Toxicology

Interview conducted by Alexander ChiltonSep 14 2015

Dr. Antonietta Gatti, Scientific Director of Nanodiagnostics, talks to AZoNano about her new book 'Case Studies in Nanotoxicology and Particle Toxicology' published by Elsevier Academic Press, 2015.

Could you provide our readers with a summary of how you became involved in the fields of nanotoxicology and particle toxicology?

It’s a very long story that I will try to summarize as much as I can. At the beginning of the 90s, when I was the director of the Laboratory of Biomaterials of the University of Modena, a laboratory I had founded years before, my husband, Dr. Stefano Montanari, brought me a caval filter, a small device which is implanted in the inferior vena cava to prevent pulmonary thrombo-embolism. That filter had broken in vivo, had been explanted from the patient and the surgeon, a friend of my husband’s, wished to know why that device had failed.

I had a long experience in implantable products and it was easy to me to understand what the problem had been. Ultimately, it was nothing particularly interesting. What intrigued both my husband and me was what I found on the stainless-steel surface of the device when I observed it through an electron microscope equipped with an EDS probe, a system that allows to detect chemical elements with the utmost accuracy.

The few remnants of blood still present contained a variety of elements that didn’t belong either to the organism or to the device and we couldn’t give any reasonable explanation to what I had found. Less than a couple of years afterwards, I received another broken filter from the same surgeon, which this time was not made of metal but of plastic instead. Also in that circumstance the surface contained chemical elements foreign both to the filter and to the organism and we couldn’t guess where those elements came from. It was only in the winter between 1997 and 1998 that we understood the phenomenon.

A patient had been admitted to the University of Modena’s hospital. For more than eight years that patient had suffered from an intermittent fever, from pain in his right ear and from lacrimation from his right eye. In addition, his liver and kidneys were seriously malfunctioning, and the only therapy his doctors had in store was hemodialysis. The diagnosis issued for him was: liver and kidney granulomatosis of unknown origin.

Due to a series of fortuitous circumstances, the biopsic samples of the diseased kidneys and liver arrived at my lab. I observed them with the electron microscope I used then, a technique no medical doctor employed, and to my surprise I found small ceramic particles in those tissues.

To cut a long story short, nine years before a dentist had implanted two ceramic bridges in that subject and those bridges were definitely ill-made. So, because of a malocclusion, they were over-worn, the patient had ingested their ceramic debris for years and those small particles had entered the blood circulation and reached liver and kidneys.

There, being bodies foreign to the organism and being the organism unable to get rid of them, they had been wrapped by and inflammatory tissue, the granulomatosis seen by the histo-pathologist, that had caused the pathology. The substitution of the two bridges and cortisone-based therapy were enough to palliate the problem so that the patient didn’t need any hemodialysis treatment.

That episode was very important at least for two reasons: one is that I saved a patient from a not particularly pleasant therapy, and two, we understood where the elements I had found years before on the two vena cava filters could have come from: probably, in those two cases, not from dental prostheses but from particles ingested somehow or, as we came later to learn, inhaled.

After that, our story became more complicated, but what is important is that in 2002 the European Community put me in charge of a research project called Nanopathology. In that contest, together with a few partners among which the universities of Mainz and Cambridge, I could research much more in depth the phenomenon of solid micro- and nanoparticles entering the organism and causing a series of conditions I called nanopathologies, since their common origin was from micro- and nanoparticles.

Then, for a number of reasons, in the year 2004 my husband and I founded the laboratory Nanodiagnostics where we are still working. One year after, the European Commission put me in charge of another research project called DIPNA based on nano-eco-toxicology, i.e. the toxicological effects of very small particles.

An-vivo image of a cluster of nanoparticles surrounded human red blood cells of a person exposed to pollution.

Could you summarise the current activity which is taking place within the field of Nanodiagnostics?

We keep researching into solid, inorganic micro- and nanoparticles and the pathologies they induce. They can enter the organism mainly via inhalation and ingestion. If they are small enough, and they often are, they reach the pulmonary alveoli and, within a few tens of seconds, they enter the blood circulation. There, in a minority of subjects, they make the blood clot, thus causing pulmonary thrombo-embolism if the phenomenon occurs in the veins, stroke and infarction if it occurs in the arteries.

In most cases, the blood carries the particles virtually to any organ, and, no matter what the organ is, it behaves like a filter, capturing the particles without any possibility for them to be released or somehow eliminated. As happens with any small foreign body, those particles induce the formation of an inflammatory tissue that becomes chronic and, in the long run, can turn to a cancer. But particles can also cause diseases of the nervous system when they are captured by the brain or, when they interest other organs, probably hard-to-suspect pathologies like, for example, type-1 diabetes if their target has been the pancreas.

Chronic fatigue, allergies and, probably, multiple chemical sensitivity, are other pathologies induced by particles. They can pass easily from mother to fetus causing miscarriages, fetal malformation or even babies who are born affected by cancer. Here I must add that the mother is healthy and is kept healthy by the fetus who acts as a sort of sponge attracting all the particulate pollutants. Another interesting possibility is the entrance of particles into cell nuclei. There they interact with the DNA during its replication inducing dramatic effects.

To answer your question, we keep researching into all those areas but, as you can imagine, research requires money and research money is not easy to come by nowadays. So, we do consultancies for criminal courts, industries and private people. Most particles are produced by human activities like car traffic, waste incineration and, in general, all high-temperatures enterprises, and we can find those particles in pathological tissues but we find them also in the environment, in food and in drugs. So, by doing consultancies, we endeavor to keep the lab alive.

What is Case Studies in Nanotoxicology and Particles Toxicology about?

Case Studies in Nanotoxicology and Particles Toxicology is the second book on the subject my husband and I have written together, the first one having been Nanopathology – The Health Impact of Nanoparticles published in 2008 by Pan Stanford Publishing, the reading of which is certainly advisable for a better understanding of what we wrote in our second book. But we also published articles and chapters in somebody else’s books.

In our first book we described the general principles of Nanopathology and the research methods we use. A chapter that attracted much interest was the one we dedicated to what we called "detective stories": six cases described from the problem as it was submitted to us to its solution. Because of the attention all that got, upon request of the publisher Elsevier we decided to write a book more focused on cases we came across and what has been published in the book contains a collection of those.

Could you outline some of these nanopathology cases to our readers?

There we offer the unequivocal proof of the pathogenicity of micro- and nanoparticles. Medicine does not enjoy the privileges of sciences like, for example, mathematics and the lucid demonstration of a theorem is not enough. Medicine doesn’t have 100% truths. Medicine needs numbers and something grows increasingly true with the increase of the number of similar cases.

In the course of our now long activity, we can offer an extensive collection of cases, some of which, the most educationally interesting, are contained in the book.  We show how one can be confronted with a nanopathology case and go back, determining its cause. If we find particles in the diseased tissue and we are good enough to be able to discover where those particles come from, we can remove them from the patient’s life or the patient’s life from them.

A section is dedicated to war cases where we show that the pathologies soldiers and, also civilians living in war territories, suffer from come from high-temperature explosion and their consequent formation of fine and ultra-fine dust.

In some instances the problems can lie in an incinerator located in the vicinity of the subject’s house, or in the job the subject does. If, for example, the patient is welder, it is not unlikely that the particles originating from the metals worked get inhaled.

Or, in other cases, as we saw, the worker goes back home with the same clothes as he wears when he carries out his job and contaminates the members of his family. In other cases it is the food the subject is wont to eat or the drugs taken. The possibilities are really manifold.

I understand that the study of a case and subsequent diagnosis generally takes a lot of time. What are the advantages of a long diagnosis period?

That’s true, this is a sort of personalized medicine. In most instances a diagnosis takes a long time or, at least, a time definitely longer than the usual diagnosis. The advantage is that it is far more accurate and many mistakes made in prescribing therapies is avoided. It is a fact that a non negligible number of patients suffer or even die from the incorrect administration of drugs and personalized medicine is much less prone to mistakes.

Another advantage is that, when a source of pollution has been identified, that can serve as a general warning. If, for example, we can see that a certain plant issues particulate pollutants, we can advise people to stay away from it as much as possible, workers busy in that plant to take the due personal precautions and the managers to remedy the problem.

In our book we describe a case of particulate pollution in a drug for nasal instillation and the pathology that pollution caused, and describe the micro- and nanoparticle pollution we found in the vaccines we analyzed. It’s true that all that takes time and labor, but, at the end, everybody, producers first, can take advantage from what has been found and prevent further problems in addition to those already caused when their origin was unknown.

Would you agree that the best way to treat a disease is to get rid of its cause?

That is what medicine should do: primary prevention. Though not always, what is generally done is to tackle a disease by administering proper drugs or, in the best of cases, by diagnosing its onset as early as possible.

We believe that that can be done and, in fact, must be done, when it is late because the pathology is already there or is coming. I don’t want to be told I’m sick before I am or be cured with the best medicaments available. I can accept that as a second or third choice. I don’t want to grow ill. That should be the aim of medicine and that is what is economically advantageous.

How much do medical doctors currently know about nanotoxicology?

Unfortunately still very little or, in most cases, much less than it would be useful to them and, in particular, to their patients. My husband wrote a number of books popularizing the subject and, paradoxically, sometimes we meet people who know much more than their doctor does!

Luckily enough, though probably with too long a delay, nanotoxicology is beginning to be the focus of articles and congresses. I am sure that in a few years it will become a discipline like many others current in medicine. Now, just to speed up the acquisition of knowledge, there are our books.

Who are your books aimed at?

They are dedicated to scientists; to nanotech technicians because they work with nanoparticles and they should know the risks they run, risks that can be avoided if they are not ignored, and they should be put in the cultural condition to know what the risks run by consumers and by general people are; to decision makers who should know that high-temperature plants produce particles harmful both for the environment and for health, to students and, of course, to medical doctors.

About Dr. Antonietta Gatti

Dr. Antonietta Gatti has an interdisciplinary background that ranges from physics, chemistry, biology, physiology and pathology. Dr. Gatti has 40 years of research experience in the field of biomaterials and biocompatibility at national and international levels in various capacities.

In 2002, Dr. Gatti was appointed as the coordinator of the European project called Nanopathology through which a new diagnostic tool was developed. The results of the project are described in her book Nanopathology, published by Pan Stanford Publishing (Singapore).

Dr. Gatti used scanning electron microscopy to identify nanoparticles in biological samples, organic matrices, in food, in water and in plants. The experience of Nanopathology led to a further European project called DIPNA (Nanotoxicology), to the Italian Projects BATNAN, INESE and VENAM of nanoecotoxicity.

Dr. Gatti is the author of about 210 articles in peer reviewed journals. She created the Laboratory of Biomaterials at the University of Modena. Currently she is a European authority in the fields of nanopathology (the human and animal pathologies triggered by micro and nanoparticles), nanotoxicology, nanoecotoxicology and environmental pollution.