The Incidental Tourist Read online

  We had plenty of time to explore. The old town of Bergamo is dominated by churches, which, along with the 1786 Angelo Mai public library, cluster around the Piazza Vecchia (old square). Science also has a place here. Embedded in the Piazza’s dark stone is the 1878 Analemma, a seven plus-metre meridian line of white marble that, covered by an arched roof, tells the time via a beam of sunlight shining through a hole in a metal plate mounted above. The adjacent seventeenth century cathedral and the twelfth century Basilica di Santa Maria Maggiore have frescoes by Giovanni Battista Tiepolo and house the tomb of a Bergamo native, the composer Gaetano Donizetti. Most would know him for Lucia di Lammermoor, a signature opera for Australian diva Joan Sutherland. An elaborate and magnificently decorated annex houses the mortuary chapel of the immensely wealthy and powerful military ‘godfather’ (Condottiero) Bartolomeo Colleoni. Born nearby, he switched allegiance back and forth between fifteenth century Milan and Venice when what is now Italy was an agglomeration of city–states.

  In 1940, the Italian Condottieri-class cruiser Bartolomeo Colleoni was sunk in the Mediterranean by the Australian Leander class cruiser HMAS Sydney. Patrolling the Southern Indian Ocean under a different captain in the following year, the Sydney got too close to the German raider Kormoran and was lost in 1941 with all hands. Though many from the Kormoran survived, the fate of the Sydney remained a mystery until marine explorer David Mearns found both wrecks seventy years later. The body of Bartolomeo Colleoni, the Condottiero not the cruiser, also disappeared for centuries till somebody looked more closely at his ‘empty’ stone sarcophagus and realised that, to avoid being disturbed, the old boy had himself interred under a false floor in the coffin!

  Also overlooking old Bergamo is the fourteenth century rocca fortress that was a home to Alpini (mountain) troops recruited from the region. The park at the foot of the castle wall has a collection of lightweight First World War and Second World War artillery that could be easily dismantled and carried through the hills. Adding to this history of arms, Bergamo is celebrated as ‘the city of one thousand’, for the central part its citizens (especially the Bergamaskers: think Carnivale!) played in the nineteenth century revolt against the Austrians (who then controlled northern Italy), leading to Il Risorgimento, the unification and foundation of the modern Italian state.

  Overall our relaxed visit with time between events was something of a respite in a frenetic year, and a heartening interlude. Apart from meeting with students and the enthusiastic organisers of BergamoScienza, there was the welcome impression that the liberal and open spirit of the Renaissance is, along with a sense of community, very much alive in northern Italy. And the automobile-free streets and stairways took us back to simpler times. The crisp, thin pizza of the region is great and, by the time the other participants left, we’d worked out where the locals ate and enjoyed a glass or two of Lombardy wine with a simple, but ample dinner of chicken, rabbit and polenta at the Al Donizetti cafe.

  Reflecting in the plainly decorated chapel dedicated to Angelo Roncalli (Pope John XXIII), who grew up nearby and served for nine years as secretary to the Bishop of Bergamo, led to the encouraging thought that, after the church reactionaries again took control to neutralise his Vatican II, the human family is once more blessed by the compassion of a ‘Good Pope’, Pope Francis, elected in 2013. And, due to luck or divine intervention (hard for an agnostic to acknowledge), there was a gratuitous reminder of the fragility of life when, walking down a narrow cobbled street, I just missed being hit by a heavy lump of masonry that fell, without warning, from high on a mediaeval wall!

  As we learned on an earlier visit to Pompeii, there is so much of archaeological value that merits preservation in Italy, and too little money for the purpose. No matter where we live, though, all of us can do whatever is in our power to preserve and protect those precious Renaissance/Enlightenment values that, by facilitating freedom of enquiry, the rise of science, democracy and civil society, have generally kept the cancer of control by regressive, authoritarians (whether based in religion, politics or personal greed) at bay. (I wrote this sentence before the 2016 US election, which has, I fervently hope, served as a wake-up call for many.) Through bright and dark times, the history of Bergamo over the past four hundred years incorporates elements of all those themes. It was a great delight to visit this living, yet mediaeval town that is not on the mass tourism itineraries.

  CHAPTER 4

  Octopus on the beach

  OFFSHORE ISLANDS MUTED BY sea-mist, breaking waves on white sand that stretches into the distance then, across the walking and cycle track, a busy highway to high-rise apartments and big hotels. Mountains behind, joggers with headphones, retirees striding out and keeping their hearts pumping while parrot-yellow spandex cocoons a very fat man who spins past on a slender racing bike. This could be early morning on a California or a Queensland beachfront, if it were not for the grazing horse, resting after hauling coconuts to the kiosk near the sign Escola de Surf. The day has just begun in Rio de Janiero’s beachfront Barra neighbourhood.

  Across the road from the ocean was the open-fronted restaurant where we had dined the previous night, now with chairs stacked on tables, unlit and lifeless. One of our party had spotted this place earlier. It was not hard to tell tourists from locals, and it was a pretty obvious conclusion that those who live nearby would know the best places to eat, so we followed them. It was a memorable and inexpensive meal: Camarones and Polvo Portugesa – big shrimp and grilled octopus tentacles with boiled potatoes, spinach – washed down with a Chilean sauvignon blanc. And, later, at the insistence of the owner, a sweet local liquor that poured like oil and caused what felt like instant shrinkage of the brain’s frontal cortex. Some of us would return later in the week to repeat the octopus experience. Others tried different dishes, but nothing seemed to equal the shrimp plus octopus.

  For that meal in March 2007, our group had explored the menu, waited for the food, and then ate and chatted. We talked of experiments and molecules, of imperial eagles, villains, heroes and literature. US President George W Bush, Bertolt Brecht’s fictional Arturo Ui (or Hitler), German Chancellor Angela Merkel, author Primo Levi and immunologist/poet Miroslav Holub all rated at least a mention. One of us had met Holub, though he was long gone, and ranked him highest for his poetry, perhaps reflecting the realities of science funding in 1960s and 1970s Czechoslovakia. Otherwise, the names that surfaced in our conversation would have been known to many intellectually aware people, and certainly to any senior biologist: Francois Jacob, Jim Watson, Albert Einstein, Richard Feynman, Louis Pasteur and Galileo Galilei. All of them wrote, or were written about, in ways that, for even the most science-averse reader, shine just a little light on the lives of those who probe underlying realities.

  The four around that restaurant table represented more than 120 years’ experience exploring the intricate and fascinating area of immunity. Why do we do what we do? What is it that makes us continue when, at least for two of our diners, we could have long been retired at a beach pretty much like this one? Saving the world? Maybe, but the real driver might be more the need for active minds to keep boredom at bay. Hooked on discovery, might some metaphorical rock we turn over as we interrogate the immense complexity of the host’s response to dangerous infections, or cancer, give a new insight, a glimmer of gold? It’s not easy to give up on questioning as a way of life.

  Living by our wits from day to day, the world of the research investigator is a bit different from what most people experience. Scientists interrogate nature for a living. What we find is occasionally of great human benefit but, though the societal reward can be massive, such work costs real money. As a consequence, communication both within science and with the general public is central to the job. We must try to explain ourselves and our endeavours to both politicians and to the broader community.

  Regrettably, and maybe this is just a personal view, too many on the conservative side of politics seem to have fallen into the trap of valuing
conviction and belief ahead of rational enquiry. Insisting on an evidence-based view and having little respect for traditionalist dogma, scientists can be seen by some as raging lefties. It is certainly the case that people who spend their lives asking questions and seeking answers don’t usually fit easily into any authoritarian worldview. When it comes to broader issues in society, the things that come immediately to the science-trained mind are: What’s the evidence? Why is he/she saying that? Are they posing (or avoiding) the right question?

  Since that evening in Rio a decade ago, the science of immunology has provided a number of novel therapies for the treatment of autoimmune diseases (multiple sclerosis or MS, and other inflammatory conditions) and cancers (melanomas, leukaemia/lymphomas). Despite those achievements, we still have a way to go in developing the understanding, and new technologies/reagents that will improve success rates. As has long been the case for small molecule (drug) and radiation therapies in cancer treatment, the achievement of better outcomes (ensuring disease-free survival) has often reflected a progression of small, incremental advances, frequently on the basis of trial and error.

  Driven by research-oriented physicians, nurses and statisticians, such work is formalised in well-planned and carefully scrutinised clinical trials. Part of our job as basic scientists is both to help with that, often by working on much simpler systems, and to make real conceptual breakthroughs. If you look, for example, behind the 2017 Nobel Prize for Physiology or Medicine that was awarded for discoveries concerning circadian rhythms (internal time clocks), you will notice that much of this work was done with Drosophila – the fruit fly.

  Stefan Kaufmann, the most practical of the four at that dinner, suggested the best we can hope for is to make things just a bit better, to lower the bar a few centimetres for those hundreds of millions living with the reality, or imminent threat, of terrible diseases. Kaufmann has long worked on tuberculosis, which still kills too many in the developing world. We speculated on whether it will ever be possible to make vaccines that protect against dangerous pathogens like TB, HIV and malaria. Pumped by the fact that his group was getting some very promising results, it’s a measure of the TB vaccine problem that, ten years later, Kaufmann’s findings are still ‘promising’. In fact, multiple drug-resistant TB now looks even scarier than it did back then.

  The immunity-based breakthrough we discussed in 2007 was with rheumatoid arthritis (RA). Based on blocking the damage caused to joints by the cytokine TNF, a molecule that operates normally to destroy invading microorganisms, this medical success (benefits to more than 60 per cent of RA patients) was recognised formally by a major award (The Swedish Craaford Prize) and knighthoods for London-based, Melbourne-educated physician/scientist Marc Feldmann and his colleague Ravinder ‘Tiny’ Maini. Their clinical trials were, of course, preceded by an immense amount of intense science done by a great diversity of highly trained and dedicated investigators with different expertise and insights. RA is classical autoimmunity, where the white blood cells that secrete TNF (tumour necrosis factor) lodge in the wrong place and respond to an erroneously delivered message that tells them to keep pumping out this powerful chemical. And this was at just the beginning of a spectrum of new immunotherapies. We could have been more optimistic, but scepticism is central to the science game.

  What brought our small group together for this dinner by a Brazilian beach was the 13th International Congress of Immunology (ICI). The 16th ICI was hosted in Melbourne more recently, in 2016, and the immunotherapy discussion had moved forward to focusing on the spectacular cures oncologists were achieving with 20 per cent of an increasing number of formerly lethal cancers, especially melanomas. As US immunologist Jim Allison (who pioneered this research) reminded us, it had taken twenty years of basic science, translation (to develop an acceptable product for human use) and clinical trials to get to this point. Jim presented his very first findings on these ‘immune checkpoint inhibitors’ in 1995, at the 9th ICI in San Francisco. That’s a typical timeline for the development of radically new treatments. It’s a dead certainty that those who attend the 17th ICI in Beijing in 2019 will present, or hear about, further major advances in cancer immunotherapy.

  Back in Rio for the 2007 conference, the efforts of the Sao Paulo-based organising committee brought some four thousand immunologists, of all nationalities, shapes, sizes and ages, together at this first ever ICI meeting in South America. Looking down as the plane banked in its early morning descent when I arrived from the United States a few days earlier, I saw blue water, miles of beaches and a soaring cathedral perched high on what looked like a small mountain. It reminded me of my hometown of Brisbane where, in the religiously polarised world of my youth, one gripe among the Protestants was that ‘the Catholics always have the hills’! The young guy who drove me from the airport wanted to talk about that other national religion, soccer. His English was a bit better than my Portuguese but, as I can’t even carry a conversation on football in my own language and he couldn’t follow my questions about the city and the local culture, we soon lapsed into silence.

  Despite the few and inevitable no-shows (people sign up at least a year ahead), the 2007 meeting was a great success. At that stage, Brazil was doing well economically and (unlike the Olympic Games) the ICIs pay their way. Rio de Janeiro offered a spectacular venue, allowing many of the speakers and participants to stay in beachfront hotels. Buses took us to the conference centre where, on the first day of the five-day meeting, workers were still dismantling some of the facilities put in place for the just completed 2007 Parapan America Games, a prelude to the 2008 Paralympics in Beijing.

  By contrast, the formal performances at a scientific conference are all verbal and visual, with a lot of PowerPoint presentations and the occasional short movie. There is, though, a certain physical endurance component for (particularly) the junior members, who take full advantage of the possibilities for partying late into the night. The Caipirinhas, the national cocktail made from fermented sugar cane juice and different fruits, tasted great but there can be the usual penalty that follows over-enthusiastic alcoholic intake. Some who had been a little inclined to party on at the Montreal congress three years earlier were no doubt forced to now confront the reality of ageing and, after a bad morning headache and a bit of blurred vision, had come to realise that they needed to take things just a little easier. As a senior citizen, it has been a long while since I made that particular discovery.

  Such big scientific meetings are great for beginners. In some cases, it will also have been the first time they have left their home country, and it would be a particular adventure to be in South America – a number headed off after the conference to tour the Amazon. The junior members got to hear key players from a spectrum of research areas, ranging across the immunology of reproduction, cancer, transplantation, allergy, infectious disease, autoimmunity, and so forth. A few of the historical figures, the ‘living fossil record’ if you like, were still around – I’m in that category. Young people will come up to chat, and I certainly remember talking to some of the eminent ‘ancients’ at the beginning of my research career.

  For those of us who are long established (I’ve attended fourteen of the sixteen ICIs), these events have less novelty, though they do offer the opportunity to get up to date in areas that we don’t know well. There’s also the chance to meet old friends from sub-fields we were once involved in but who are no longer participants. Way back, for instance, I used to go to transplant and MS meetings, but I’ve long since moved out of both areas. We are reminded of the inexorable passage of time as we run into former colleagues we haven’t seen for years. I recall one senior brain researcher who, previously an incisive intellect, was clearly impaired by the loss of intellectual capacity that hits 50 per cent of all human beings by their ninth decade. At these big meetings, it’s almost inevitably the case that familiar figures we might expect to see from other fields are either unable to travel or have passed on.

  In 2007 an old frie
nd, Eli Sercarz, was dying of cancer. I hadn’t heard that Eli was ill, and was shocked to see him. Frail beyond measure, he broke an arm during the meeting but turned up for the closing ceremony after spending much of his time promoting ‘speaker’ lunches, where those starting out got to meet personally with leaders in the field. Mentor to the end, he understood that continuity is important and that we can only go forward. We said our farewells, knowing that we would not meet again.

  After seven days of lectures, parties or dinners every evening, including two days of committees to do with the International Union of Immunological Societies (I was President for three years from 2007), enough was enough. Though sorry to part from the experience of walking on the beach (and feeling quite safe) at dawn before the burning sun breaks through, then breakfasting on papaya and mango, and bacon and eggs and coffee and not having to wash up, and then listening to innovative science and having intriguing conversations, it was time to move on. The trade exhibits were packed back into their boxes and the venue soon emptied. The organisers could at least relax, pleased that there had been no major disasters.