01-12-2013 - Traces, n. 11

new world

Outside the Comfort Zone
A fascination for the work and life of his medical predecessor, Jerome Lejeune, inspires the ground-breaking trisomy 21 research of DR. PIERLUIGI STRIPPOLI. In this interview he describes the myriad surprises of a promising career diverted to a new path through unchartered territory that produces “real” therapies for Down patients.

by Suzanne Tanzi

In 1866, John Langdon Down was the first to specify a similarity in facial features–resembling those of Mongoloid decent (hence the designation “Mongoloids”)– among the broad cross section of people with intellectual disabilities.  No further studies were conducted for those placed in this category until, almost 100 years later, Dr. Jerome Lejeune –the “Father of Modern Genetics”–diagnosed that these cases all exhibited an anomaly in the 21st chromosome. One of the leading scientists in the field of trisomy 21, or Down Syndrome, is Dr. Pierluigi Strippoli, Associate Professor of Applied Biology, Department of Specialized, Diagnostic, and Experimental Medicine, at the University of Bologna. He met with Traces to discuss his shift of career, the fruitfulness of being both a clinical doctor and a researcher, and the primacy of reality in medicine: “Experience as a source of knowledge is crucial.”

After graduating in 1990, you pursued your PhD and post doc in experimental hematology and then, as a researcher, you taught genetics. How did your promising career in hematology get diverted into trisomy 21 research?
Dr. Maria Zanotti , a former fellow of Dr. Lejeune and a teacher in my program, asked me to collaborate in trisomy 21 research because I had acquired some useful new study skills. But I did not want to move out of my comfort zone. Dr. Zanotti’s passion for the subject was contagious, though, so I began work on chromosome 21–where I stayed for ten years. Over those years, our lab grew from two  people to ten, but each year it was less and less about Down Syndrome and more on chromosome 21 in general and as applied to other conditions. Developing therapies for actual Down patients–whom I had yet to meet, by the way–was a remote consideration. At the end of 2010, I was looking at moving into any kind of work other than that of trisomy 21.

What inspired you to change your plans (again!)?
Quite by chance–beginning with a car ride to the airport, actually–I met a few doctors through whom I got to know more about Jerome Lejeune, the unity of his person, not to mention his incredible results, his persecution, and his beatification process. These new friends, Mark Basik and Ombretta Salvucci, pressed the point further and, once again drawn in by someone else’s certainty and enthusiasm, I agreed to go to the Jerome Lejeune conference in Paris, even though I was finishing up my research in this area and determined to move on.

What happened there?
Well, imagine the scenario…  Just 2 weeks before the trip, before my “ruin” began (!), I was thinking of everything but Down Syndrome. But suddenly I was invited to the home of Lejeune himself. It was a shock. I could never have imagined it! The most casual circumstances brought me to this point–a person riding in my car...  While I waited for dinner to be ready, I perused the books in the study and was astonished to find so many on general informatics. He was a prophet: he had already insisted that it be studied in conjunction with genetics decades before, while we were only just realizing how much bearing informatics has on genetics. In Paris, I met the person of Jerome Lejeune, through a look at how he lived and in meeting his family, especially his daughter Clara and his wife Berthe. They told me that following his death, the volume of letters and witnesses they received led Berthe to pursue the work and witness of her husband–and she had so much to do for this! Looking at Jerome’s  photo, she says,  “Don’t you think you are exaggerating?! Don’t you see how much work you are giving us?!” And then, Berthe asked all about my work and she concluded: “You must go see patients!”

How did you respond?
I said I had not seen any patients for 22 years! Again, I did not want to venture too far out of my comfort zone. But I could not deny that I was intrigued by her invitation. Still, for almost a year, I held off. The last straw was attending the Mass of the closing of the diocesan process of beautification for Jerome Lejeune in 2012. It was such a beautiful thing for me that I took out my white handkerchief, waved it, and surrendered!

How did you start over from there?
I had to go “back” to clinical, as a student, going on rounds with doctors to see the patients with other med students–even though I myself had sat on the exams of many of these doctors! Then, completely out of the blue, a doctor I never met asked me to help oversee 130 Down Syndrome patients. From there, uniting clinical studies with our lab research, we began a new line of work. From my lab of ten people, three came with me, and after two years we now have a staff of five.

You took a risk…
Yes, a very worthwhile one. I am now convinced that all researchers must see patients, as Madame Lejeune had insisted with me. Watching what goes on in clinical reality provides a more complete information base to work with.

Can you give some examples?
 I discovered that the gravity of the cognitive impairment was less than what we researchers were writing about–this shows that the ability to measure intelligence is compromised if you are not spending time with the person. For example, it can be reported that a patient cannot understand this or that, but then you see for yourself that they do understand, they just cannot express themselves.  There was one boy who became unhappy when children’s music was playing–one might jump to the conclusion that he has not the faculty to appreciate music. But he was actually and consistently indicating other CDs he did want to hear–by Queen and Bruce Springsteen! His musical taste could be said to be ahead of that of his peers. It seems that music is a more immediate conduit to the heart than words are, so you do often find these kids very drawn to it.

What other gifts have you observed in this population?
According to Lejeune, the ability to admire is the highest human expression –to contemplate a sunset, to recognize beauty–and the fact is that those with Down are frequently in such a happy state of awe before the world. Another remarkable quality is their capacity to elicit our affection; they make us all feel better, happier. They bring the gifts of love and unity to a family–the testimony from parents on this is irrefutably beautiful and strong. Then, each has his own and diverse talents, just like all kids.

Ninety-percent of diagnosed Down Syndrome pregnancies in Europe end in abortion. Many argue that the quality of life will be compromised...
Of course there are very profound challenges and these cannot be overlooked. But again, something greater shows itself when we observe, whether it is in the form of the unique gifts of the person with Down, or in the form of what it awakens in those around him or her. Also, studies show that 95% - 99% of those afflicted are satisfied with themselves and with their family. This percentage is much higher than the norm–in short, they are more happy than the average person. When in doubt (as I was) you need to meet the families and the children themselves. Otherwise, your ideas are abstract; you imagine the worst. Experience as a source of knowledge is crucial.

These facts were observed 50 years ago by Lejeune himself. Is there some value in going back to his original research notes?
It is very unusual for scientists of today to find any value in old research articles and conferences–they are always outdated. But going back to Lejeune’s notes, I find the information so fresh and current. This is because he was always projecting outcomes. He also united disciplines–for example, he even had philosophical writings on human intelligence. In a dualistic world, he shows us how to be a “complete” scientist.  He is still current because he never reduced the field to a small sector but always reasoned at once as a biologist, physician, chemist, philosopher–simply remarkable.

How has this affected your technical work of today?
We are trying to unite clinical research, chemistry, cytogenetics, genomics, and bioinformatics (computational biology) for a therapeutic result. And I have succeeded in restricting the importance of the mouse model in this field of research. Starting from clinical behavior, the genetically engineered Down Syndrome mouse is useless, and this was, in the past, what was driving our research. The mouse does not have the reasoning level typical of man.  My  favorite poet, T.S.  Eliot says, “I must remind you that a dog is a dog and a cat is a cat.” And I say, “I must remind you that a mouse is a mouse and a man is a man” !

Is it true that your research is the only one that is working with human cells? Where is it leading?
I am the only researcher (I know of) in this field who is deeply involved with the clinical. There are very few groups merging the two fields at the level of our current project. We will correlate our investigations of patients with DNA and RNA lab studies. Collecting clinical data from 130 patients will affect not only our ability to offer therapy for Down Syndrome but also our understanding and treating of other diseases–such as celiac disease and others stemming from the 21st chromosome. Relating symptoms and diseases, we can address them better.

How do you face the seemingly overwhelming challenges ahead?
Sometimes, I feel like Berthe Lejeune, gazing at her husband’s photo and complaining, “Don’t you see how much work you are giving us?!” But I am very excited about it. Before, I was searching for a technical cure for Down Syndrome. Now, I am looking to improve the lives of Chiara and Davide and all the others I know by name.