Unpublished

If the genome is, with a fair approximation, the cookbook with the recipes for all the components that make up our organism, researchers are finally able to browse the entire book and even to recognize single phrases and chapters - genes and chromosomes, respectively. At least, this was the good news that came with the publication of the final draft of the human genome. The bad news (or not, depending on your point of view) is that, when it comes to understand how the genome works, the DNA sequence is only part of the story.

The genome draft has showed that humans have between 25.000 and 40.000 genes, only about three times as much as the fruit fly and almost as much as the thale cress, a small plant, simpler organisms that, as far as we know, are not able to write or send spacecrafts to the moon. It is now clear that what makes the difference between Einstein and a banana is not the number of genes but their type and probably, the way they are regulated. Moreover, 95 per cent of our DNA does not code for any protein, and it’s hard to think that all this information, which every cell painstakingly passes over to its descent, is just “junk”- as it was dubbed in the past. Indeed, in recent years researchers have found that the genome has a layer of complexity bigger than just the sequence of letters contained in the genes.

They called this type of regulation epi-genetic ( literally, “sitting above the genes” ) because it does not affect the content of genes but, instead, decides if and how they will be switched on, read by the cellular machinery and eventually traduced into proteins. This brings an enormous level of complexity to the genome: each gene has a unique DNA sequence but can have potentially infinite epigenetic states.

Scientists are accumulating evidence that epigenetic phenomena play a critical role in normal growth, functioning and aging of the organisms. Faulty epigenetic mechanism are also suspected of contributing to a variety of diseases. The Online Mendelian Inheritance in Man (OMIM), a database of human genes and genetic disorders, lists more than a hundred ailments where epigenetic mechanisms are involved or strongly suspected. Some are rare, such as the Facio-Scapulo-Humeral muscular dystrophy, the Prader-Willi, Angelman and Beckwith-Wiedemann Syndromes, but the list also includes common diseases such as cancer and diabetes. By looking at the “dark face” of the genome, the study of epigenetics could suggest new strategies to treat these disorders.

There are several known epigenetic mechanisms, and many other are probably to be discovered. Methylation, a chemical modification by which an hydrogen atom is replaced by a small carbon compound called methyl, is a well studied mechanism that cells use to earmark portion of the genome: when methyl groups are added to a gene, this usually means “this gene is locked up”. It is a bit like stapling or gluing together the pages of a book: the information itself, stored in the print or in the DNA, is unaffected, but has become impossible to access. RNA, a working copy of the DNA that transfers genetic information in the cell like a computer diskette, is emerging as another fascinating actor of epigenetics. Antisense RNAs (anti-copies of genes that can block their information) and non-coding RNAs - both thought once to be useless- have been instead found to regulate the activity of thousands of genes and even of entire chromosomes.

A sophisticated mixture of methylation and RNA-mediated “silencing” is responsible for blocking one of the two X chromosomes of females. Epigenetics also explains a genetic phenomenon called imprinting, where a trait becomes apparent if it is inherited from the mother and not from the father, or vice versa. For example, the Angelman syndrome, a rare genetic disease caused by the loss of a portion of chromosome 15, will manifest only if the defective chromosome comes from the mother. The same defect, but on the paternal chromosome, will curiously cause a different disease, the Prader Willi syndrome. Researchers have found evidence that this happens because the maternal and paternal versions of chromosome 15 are imprinted in different ways. Epigenetic defects also contribute to the genetic chaos that leads to cancer. In fact, some experiments suggest that methyl-removing drugs could be useful to treat a form of leukemia and maybe other types of cancer, in which tumor-suppressor genes are blocked by methylation.

Stem cell research and cloning could benefit largely from advances in epigenetics, too. Imprinting has an amazing capacity to wipe out and restore itself during development: soon after an oocytes is fertilized, nearly all imprinting is removed from the chromosomes but is then re-established during gestation. Researchers agree that most clones obtained in the laboratory fail to develop properly because they miss this important, and still mysterious, “reprogramming” step. Adult stem cells, too, must go trough a similar reprogramming process before they can transform themselves into different types of tissues and be used in therapy.

The exploration of the heretofore invisible side of the genome has just begun. One day, the consequences for the understanding of our biology and for our health could be huge.

Copyright Sergio Pistoi  All rights reserved

As a scientist, there are endless occasions where you are called to speak about your work or to give an expert opinion on scientific subjects.

• Can you be simple and accurate at the same time?
• Can you condense your message in a few words?
• Can you get your story  across, involving the lay audience and the press?

FROM BENCH  TO PUBLIC is my communication and media training workshop tailored for researchers and science/medical professionals.

The approach is very interactive and entertaining and includes many activities  and role-plays that will show you the do’s and don’ts of communicating science with the public and the media.

WHO ARE YOU TO DO THAT?

I am an experienced and passionate science writer who was a former researcher.I will  not lecture you: before  I moved from research to science journalism, I did all the mistakes that scientists do when dealing with communication. Now, I think I’m in a good position  to  help you  avoid most of such errors.

WHAT IS THE LENGTH OF WORKSHOPS?

A typical workshop is about 2 hours-long, which includes some practical activities. A longer workshop (3 hrs to one day) allows a “full immersion” with many individual and groups activities. I also do introductory seminars of about 1h30.

The time and focus of the program can be tailored according to  your needs and interests.

WHAT CAN I DO TO PARTICIPATE?

You can invite me  to do a workshop/seminar in your institution or venue (congress, convention, course etc..) or as a part of a course.

I do not currently organize my own venues, therefore I have to turn down requests from individuals, unless they can arrange to make a group and provide a suitable location.

HOW MUCH DOES IT COST?

The cost depend on the type of workshop and on how far is the location. Anyway, my requests are always very reasonable. Feel free to contact me for any information.

WHICH ARE THE LANGUAGES?

I do the workshops in English, Italian and French. I can travel almost everywhere.

DO YOU HAVE HANDOUTS FOR THE PARTICIPANTS?

Yes.

WHERE IS A LIST OF YOUR PAST WORKSHOPS?

An incomplete list is here.

Photos were taken during Biopop workshop in Bologna. Courtesy: Biopop.

My skinning of the beast started in 1997. I was back to a lab in Italy after my Ph.D. in molecular biology in Paris. Like all my postdoc siblings, I spent long days surrounded by mice, pipettes and all the paraphernalia of the modern molecular biologist.

At night, when most of my colleagues where peacefully lying on their sofa, or engaging in more grooving nocturnal activities, I morphed into a writing Mr Hyde. Earlier that year, I had made my first step into science writing by unmercifully harassing the editors of an Italian science magazine until I got my first assignement. A few months later, took more courage and successfully pitched a couple of news stories to Nature and The Lancet.

My double life was becoming interesting but also difficult to match with my research career, the sanity of my neurons, and the sparse social interactions with non-rodents. It was time to make a choice.

I turned down a sweated-out fellowship renewal. I made sure that my transition was as smooth as possible for my colleagues and the research project. Then, I bought a PC, fax, modem and a new desk and I set up business in my home apartment. I found out that the best survival strategy was to be creative and keep my range as broad as possible. I made a list of all the science book and magazine publishers in Italy and sent my CV to all of them. If not luck, at least statistics would be on my side. A few answered. I worked as translator, as a ghost writer, as a reviewer for science books.

I also contacted Telethon Italy, the charity that financed my post-doc, and I proposed them to set up a website that would provide information to patients about genetics and hereditary diseases. They liked the idea and signed me up. The website (www.informagene.it) is now a national reference in its field. It was the start of a rewarding and long (still ongoing) collaboration with the Telethon, a world-class and dynamic research charity.

A few years later, another turning point in my carrier was the internship at Scientific American in New York. It was one of my greatest and more enriching professional experiences. Unexpectedly, I fell in love with the Big Apple. I still try to go there as often as I can. The next year, I was awarded a journalistic fellowship from the Armenise-Harvard Foundation to the Harvard Medical School in Boston.

That’s the way I started. it’s just one of a zillion possible starts (and probably not the most straightforward), but I hope that my experience will be helpful to those who are considering a career into science writing.

A piece of advice for a carrier switch? Here you go: if you are a scientist, don’t think of science writing as an easier alternative to research. Like research, journalism is a difficult and extremely competitive world. I also found out that a research background can be very useful, but is not essential. I usually cover the fields where my research experience and my sources are most valuable: biomedical, genetics, stem cells and “hot issues” such as cloning, biotech, GMO and research policy. When I deal with these subjects I prefer to do fewer but longer, in-depth stories than many shorter ones. However, I don’t like to be over-specialized and I try to keep my scopes broad. I cover IT, geography, physics. I am always open to explore new territories and I love to travel.

Finally, I am often asked if I miss the laboratory. The answer is: yes, I do miss the laboratory. Perhaps this is why I choose to devote a large part of my activity to the monitoring and strategic planning of research, which I do for Telethon. Together with science writing, this is an excellent way to be a part of the scientific community. When I miss the sound of the centrifuge, the long arrays of minitubes on a rack, the smell of phenol, I can still pay a visit to one of my many lab-rat friends.

Spektrum der Wissenschaft (German edition of “Scientific American”), Jan 2006

Scientific American, May 2004 Read it

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Scientific American, February 16, 2004 READ IT

New Scientist, June 16, 2003 [READ IT]

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New Scientist 21 December 2002

A brave new step for medicine as an organ is treated outside the body

New Scientist vol 176 issue 2374 - 21 December 2002, page 7

FOR the first time, cancer has been treated by removing an organ from the body, giving it radiotherapy and then re-implanting it. The out-of-body operation allows doctors to administer high doses of radiation to widespread tumours without affecting other organs.

Doctors in Italy used the technique to treat a 48-year-old man with multiple tumours in his liver. One year after the operation, which took 21 hours, the man is alive and well. His liver is functioning normally and the latest scans have not revealed any signs of tumours.

The team, which consists of surgeons at the San Matteo Hospital in Pavia and physicists from the local division of the National Institute of Nuclear Physics, is now waiting for approval to treat another six patients with multiple liver tumours. If these are successful, the technique could one day be used to tackle hard-to-treat cancers in other organs that can be transplanted, such as the lungs or pancreas.

The patient they have treated had had a colon tumour removed, but the cancer spread to his liver. Scans revealed no fewer than 14 tumours there, and many smaller ones were discovered during the operation. Such diffuse cancers are very difficult to treat by conventional means. The tumours proved resistant to chemotherapy. And there was little hope of killing such widespread growth with conventional radiotherapy - which usually involves focusing X-ray beams onto the target - without destroying the liver.

So doctors decided to try a method called boron neutron capture therapy, first attempted in the 1950s, in which boron atoms are attached to the amino acid phenylalanine and injected into a patient. Because they are growing quickly, tumours take up more of the compound than normal cells. The team has been working on the method since 1987 and has done extensive studies to work out the optimum dose. Two to four hours after the compound is given, a low-energy neutron beam is directed at the organ, splitting the boron into high-energy particles that mainly kill the cancer cells.

But to ensure that all cancerous cells are destroyed, an even dose of neutrons has to be given to the entire organ. That’s not easy to do in the body, where obstructions such as bones block the neutron beam. And the tissues surrounding the organ inevitably receive a large dose of radiation.

Instead the surgeons decided to remove the entire liver. The organ was placed in a Teflon bag that neutrons can pass through and taken to a research reactor nearby, where it was irradiated with neutrons. It was then re-implanted, just as in a normal liver transplant operation.

“By explanting the organ, we could give a high and uniform dose to all the liver, which is impossible to obtain inside the body without serious risk to the patient,” says Tazio Pinelli, a physicist who coordinated the work together with liver surgeon Aris Zonta. “It was a bold stroke and has stirred the interest of many in the field,” says Paul Busse, a neutron radiology expert at Harvard Medical School in Boston.

The technique has been dubbed TAORMINA after the Italian for “advanced treatment of organs by means of neutron irradiation and autotransplant”. But with only one person treated so far, it is too early to judge how safe and effective it is.

Even if the method proves effective against liver and other cancers, such a drastic operation would be reserved for patients with the worst outlook, and could only be carried out while they were still strong enough to survive the long operation.

It could also be used only in cases where the spreading cancer is restricted to one organ. Once cancers spread widely, there is little that can be done. Another problem is that there are few reactors capable of producing suitable neutron beams.

But the work could also help improve normal boron neutron capture therapy, Busse says, by improving our knowledge of what doses are safe and effective. The technique is currently being tested on patients with otherwise untreatable brain tumours - obviously without removing the organ in question. Sergio Pistoi, Rome

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