RESSONÂNCIA 8th AIMS Meeting edition

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PROGRAM

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Editorial

“I like the scientific spirit - the holding off, the being sure but not too sure, the willingness to surrender ideas when the evidence is against them: this is ultimately fine - it always keeps the way beyond open - always gives life, thought, affection, the whole man, a chance to try over again after a mistake - after a wrong guess.”

Walt Whitman, “Walt Whitman’s Camden Conversations”

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Index

editors Ana Raquel Estalagem Ana Brochado Catarina Paias Gouveia Joana Cabrita José Durão José Rodrigues Sérgio Bronze

HUMANITARIAN MEDICINE & INFECTIOUS DISEASES

staff Ana Lúcia Fernandes Ana Sofia Mota Catarina Nunes Catarina Relvas Cláudia Silva João Bastos João Martins Jorge Rebola Mafalda Jorge Miguel Antunes Nuno Fernandes Pedro Félix Rita Enriquez Tiago Grohmann Pereira design Ana Dagge José Rodrigues printing and property

07 | Those whom the world tends to forget 08 | Dr Tough 09 | The micro rebellion 11 | Keynote: A determined woman, a caring doctor and a passionate teacher

SURGERY

13 | The history of surgery 14 | Can robots turn into surgeons?

15 | Face transplant: a real solution or a deviation from the real problem?

17 | The bionic eye 18 |Keynote: The Health Error

ONCOLOGY

20 | Russian Roulette 21 | CRISPR, a new dawn for genetics?

23 | Interview: Bruno Costa-Silva 26 | Keynote: Translational Medicine

CULTURAL & CHARITY PROGRAM

Editorial Section of Associação de Estudantes da Faculdade de Medicina de Lisboa editorial@aefml.pt Associação de Estudantes da Faculdade de Medicina de Lisboa Avenida Professor Egas Moniz, Hospital Santa Maria - Piso 01, 1649-035 Lisboa 217 818 890 | ressonancia@aefml.pt www.aefml.pt facebook.com/ressonanciaaefml Legal Deposit: 178455/02 Print run: 800 copies Distribution: free

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Opening Message Dear Participant, First of all, I would like to welcome you to the 8th AIMS Meeting.

In this introductory note to the AIMS Meeting edition of RESSONÂNCIA, I would like to leave you with three messages: one of knowledge, one of righteousness and one of happiness.

In an ever-changing, fast-paced, complex world, being a Health Professional goes far beyond being a highly trained technician in the art of diagnosing and treating illness. One must be able to navigate the murky waters of the medical world, where threats lurk from all sides. The needs and wants of one’s patient, the demands from the hospital administration and the relations with those who have a business in one’s decisions, must all be balanced correctly. None is so important that it must prevail in every situation, and none is so insignificant that it needn’t be heard.

The voices of sailors and the allures of mermaids are hard to tell apart, when sailors and mermaids are simply metaphors to people who look the same, work in the same building, do the same kind of job, and, not uncommonly, are the exact same person. Doing the right thing is very hard in a world when we very often don’t know what is wrong. It requires a profound knowledge of the night sky and a very strong compass – a moral one.

My first message is this: hold, with every step you take, the knowledge of what is right. Do not let the voices of mermaids lead you astray, for they do so without your knowledge. They frequently do not corrupt your soul, and that is their evil power. You will not know that you are doing wrong, while doing it. And you will be held to your actions as if to the pole of your ship, and you will go down with it, because you had the duty to hold the knowledge of what is the right path in the open bright blue morning sea, and you did not. You were an ignorant fool. Ignorance, and not wickedness, is the doom of the everyday man.

But not every sailor aspires to merely sail well. Some know which paths are wrong, but decide in favour of following them in search of great treasures they hear of in the voices of mermaids. This is certainly not the path you set out for when you left harbour. Remember you have a duty to yourself, to all those who depend on you and to Humankind. This is my second message: hold, in every step you take, the memory of the route you set out for when you lifted sail. The route of righteousness. Remember that the ideals that guided your heart back then are every bit as valid now and even more. Wickedness, and not ignorance, is the doom of those who do not want to be everyday men.

In this small country planted by the sea, think of Lisbon as the departing port for your journey as a Health Professional.

Learn your craft, gather your tools and embark on the ship you built. Have a safe travel. Know which tides are good and which lead to annihilation, and remember why you mustn’t follow the wrong ones. Know which are the sailor’s warnings and which are the mermaid’s songs, and listen only to the ones which do not fool you. Be knowledgeable and righteous.

Happiness is only a consequence of that.

Enjoy the congress.

Kind regards,

Filipe Peste Martinho, General Coordinator of the 8th AIMS Meeting AIMS Special Edition • 5

across boundaries

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Those whom the world tends to forget AUTHOR

Rita Enriquez

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orld, 2017. Ours are frantic times.

Days are intense, fast, people are impatient and live absorbed by their own lives, with absolutely no time to just stop and look around. Humanity cries out for help. It’s a deaf scream, violent, desperate, heard by many and yet listened by so few.

We live an unprecedented humanitarian crisis. A shallow war that devours people, families, entire nations. And with it, a sort of ozone hole that grows within human rights and stubbornly keeps on being ignored, while millions of people lose everything they have and are: their health, their dignity, their life.

Health. A word that implies such a broad meaning, a human right that we all should have, yet only some possess. We’ve gotten used to it, in these so-called developed countries, to this comfort and safeness that we tend to underestimate, to a certainty that health resources will always be there, available to answer our problems at any time. But what if, by any chance, not everything was that granted? What if we crossed to the other side of meridians, what if we flipped the coin? What would happen to these nations, so self-assured, so adapted and prepared for adversity, if it unexpectedly occurred - natural catastrophes, pandemics, a terrorist attack, a world war? Would we be ready to face the destruction, the separation and the loss?

It is a rather difficult answer for those who’ve never lived a similar experience; it is difficult to put ourselves next to someone in such extreme conditions and manage to fully understand the pain, the despair.

However, difficult does not necessarily equal impossible. In fact, we as individuals and, most importantly, as future doctors, should be able to put ourselves in someone else’s shoes and experience how that someone feels. This ability goes far beyond mere empathy, it is deeper than that. It’s an extraordinary skill combined with a deeply embedded altruism, that is not attainable by everyone, but to those who allow themselves to renounce to their own personal interests in order to practice medicine in conditions that are far from ideal, aiming purely and solely to help others in need.

These humanitarian physicians, real doc-

“Life’s most persistent and urgent question is, ‘What are you doing for others?”

Martin Luther King Jr. tors of catastrophe, take off their layers of (home) comfort to invest themselves in an almost parallel world of devastation, where hopelessness reigns.

It is a much less recognized work than it should be, that of those who backpack their own lives to receive others’ lives in their arms, those who embrace this great journey as their mission - to save lives, alleviate suffering and promote human dignity.

Their work goes far beyond treating an infection, malnutrition or amputating a limb. These doctors carry within themselves a psychological and spiritual ointment to the sick. For people that have lost their families, their achievements, their own meaning; people that often only exist, perpetuating themselves in time for as long as they are allowed, without actually living; for those people, doctors are much more than mere physicians, they mean hope and faith, they are a ticket to a new beginning.

Humanitarian Medicine is much more than the therapeutic act per se.

It promotes and provides healthcare to populations as a human right, to which we should all have access without restriction or discrimination. The practice of medicine in its most ethical and pure aspects, without thinking of ulterior benefits besides the well-being of people as a whole, spread by this exceptional group of professionals, restores my hope in the humanity of a Humanity that I’ve lately seen fading out. These people are the living proof that there is still respect for the original values of Mankind.

Each one of us has the duty and the privilege to change the world. It’s up to us, the next generation of physicians, to carry the values we’ve learned and which define us as human beings across borders, not only the physical ones but those borders between people, between cultures. It’s our mission then to restore not only health, but also hope in everyone we cross, especially in those whom the world tends to forget.

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Dr. Tough Bringing hope to the land of nothing.

AUTHOR Tiago Grohmann Pereira

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ur World is made up of a multitude of lands, each one holding millions of people that often fail to live side by side or become critically affected by natural disasters.

MSF, Médecins Sans Frontières / Doctors Without Borders, was born in the 70’s, after a french group of doctors and journalists, working with the Red Cross, witnessed the human atrocities at Biafran War and decided that they wanted to do more. Nowadays, almost 50 years later and being 90% funded by individuals, MSF enjoys an unmatched level of independence that allows it to be the first humanitarian organisation to arrive at the scene of a major incident, provide impartial emergent care and, often, the last to exit it, once everyone has been evacuated.

Lavish Land On our corner, the story is incredibly different. Our basic needs are the same as of those in underdeveloped countries, only chance had us born within a privilege social context. Mild weather that whispers on our window, wealthy pockets and educated minds to read this from the comfort of our welllit lives. When wifi is weak, we let it lag our souls. When we face a problem, we often react in vain complaint, rarely resourcing towards a solution. Our hard work, our endless hours of study, for so many years, feel too much for one to consider choosing a career demanding more sacrifices and emotional strain.

Disaster Land This month, famine was declared in

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South Sudan. The formal announcement means that people have already died from this man-made disaster. Yemen and Nigeria wobble at the brink of one alike and Syria still deals with the hoard of third parties ravaging the lives of the country. MSF works in 60 countries where malnourishment and illness spread at the speed of bullets, where development is held stuck in swamps of corruption.

The staff, composed in its majority by local people, fight daily for survival in the aftermath of disasters, some of it natural but often wars externally financed. We live in an age where we are appalled at the notion of weapons being sold to children or people suffering from mental illness but we don’t question the profits made by our nation’s arms industry, feeding far more deranged criminals that step over Geneva convention to purposely target field hospitals and torture.

MSF Mindset To survive in these conditions, MSF has resourced to undercover facilities where they are able to carry out essential treatment without risking the lives of their staff, appealed to the UN council to strengthen support and resource to telemedicine, providing care when no one else does.

After being selected, a MSF doctor is expected to work for a period of 9 to 12 months in a low-risk area, to begin with.

Here, abiding by the protocols is much more than a Bee Gees tune. Staying alive and caring for the safety of your team requires a strong sense of hierarchy, humbleness and fine-tuned negotiation

skills between your values and goals and those of the hosting country. This will impact how effective you are able to provide the human rights that most of us lack.

Going into a mission will be just as difficult as coming back home. If on arrival you might need to adopt a camping lifestyle, endure months on end with crewmates that you must get along; when returning, it’s possible to feel disconnected from your peers, from your own culture and society. Despite this, if psychologically well grounded, supported by your closest network and accounting with a flexible employer, working with MSF will make you a more rounded person and definitely a more experienced physician.

One Land The safety of people living in underdeveloped countries is just as important to us as our own safety and health care in our own backyard. The curtain lies now flat on the stage. Behind it, a planet far more connected than before, reveals how infectious diseases can quickly threaten our lives; how wars waged in distant lands, expel the suffering of millions of refugees into our countries.

The political powers still try to build higher walls. They believe that by separating us we can be safer. We are clearly in need of wiser politicians as much as we need brave physicians to bring hope to those who lost everything.

Only by caring for the well-being of all, will we truly gain the sound prosperity that we look for yourselves.

The micro rebellion AUTHOR

Ana Sofia Mota

T

he 22nd of March 2014 was a black Saturday for the world of Health.

The WHO reported the first Ebola cases, revealing the largest and most complex outbreak since the discovery of the virus in 1976. Despite a relatively low pandemic potential, the inexistence of a cure or vaccine combined with a fatality rate around 50%, makes Ebola one of the scariest transmissible diseases of the last years. The most severely affected countries, Guinea, Liberia and Sierra Leone, have very weak health systems, lack human and infrastructural resources, and have only recently emerged from long periods of conflict and instability. Therefore, Ebola has its magnitude, transcendence and vulnerability, meeting all the criteria that led the WHO Director-General to declare on August 8 the West Africa outbreak a Public Health Emergency of International Concern under the International Health Regulations (2005) and the alarm bells rung worldwide. Fortunately, only panic and awareness of the necessity to have effective contingency plans spread, raising the big question: is the world prepared to deal with a pandemic?

As said by the WHO, emerging and re-emerging epidemic diseases pose an ongoing threat to global health security.

The Twelfth General Programme of Work 2014-2019 targets “reducing mortality, morbidity and societal disruption resulting from epidemics through prevention, preparedness, response and recovery activities” as one the Organization’s five stra-

tegic imperatives, which is a responsibility • of the Department of Pandemic and Epidemic Diseases (PED). This unit develops mechanisms to address epidemic diseases, thereby reducing their impact on affected populations and limiting their interna- • tional spread. The goals are the following: •

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Improve the evidence-base for epidemic diseases, in order to inform national and international decisionmaking Protect communities through timely risk assessment, monitoring and field investigation of epidemic diseases of international concern Support countries throughout the epidemic cycle: Preparedness, Response and Resilience to epidemics Optimize health care to reduce mortality Establish and manage global mechanisms to tackle the international dimension of epidemic diseases

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Airborne diseases: influenza (seasonal, pandemic, avian), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome coronavirus (MERS-CoV) Vector-borne diseases: yellow fever, chikungunya, Zika fever, West Nile fever Water-borne diseases: cholera, shigellosis, typhoid fever Epidemic meningitis Rodent-borne diseases: plague, leptospirosis, hantavirus, Lassa fever, rickettsia (murine typhus) Haemorrhagic fevers: Ebola virus disease, Marburg virus disease, Crimean-Congo haemorrhagic fever, Rift Valley fever Monkeypox, Smallpox Other zoonotic diseases: Nipah virus infection, Hendra virus infection Any other emerging disease

There is also a special programme for antimicrobial resistance and influenza has its own “Pandemic Influenza Preparedness Framework”. This fact consolidates these subjects prospectively as the two major threats. On one hand, new resistance mechanisms are emerging and spreading globally, threatening the ability to treat common infectious diseases, resulting in prolonged illness, disability, and death. Without effective antimicrobials for prevention and treatment of infections, medical procedures The list of the main epide- such as organ transplantation, cancer mic and pandemic diseases is not chemotherapy, diabetes management short, englobing several categories: and major surgery (caesarean sections

«emerging and reemerging epidemic diseases pose an ongoing threat to global health security.»

AIMS Special Edition • 9 ressonância

or hip replacements) become very high risk, increasing the cost of health care with lengthier stays in hospitals and more intensive care required.

Single, isolated interventions have limited impact, so, as coordinated action is required, all countries need national action plans on AMR. Greater innovation and investment are required in research and development of new antimicrobial medicines, vaccines, and diagnostic tools. On the other hand, a pandemic influenza occurs when an influenza virus which was not previously circulating among humans and to which most people don’t have immunity, emerges and transmits itself among humans. These viruses may emerge, circulate and cause large outbreaks outside of the normal influenza season. As the majority of the population has no immunity to these viruses, the proportion of people in a population getting infected may be quite large. Some pandemics may result in large numbers of severe infections while others will result in large numbers of milder infections, but the reasons behind these differences are not completely understood. The most notorious pandemic for which data is available is the “Spanish Flu” in 1918-1919, which caused an estimated 20-50 million deaths worldwide. Subsequent pandemics in 1957 and 1968 being susceptible to infection. In 2009, a strain of influenza A (H1N1) virus which had not ever been seen before, emerged, spread across the world and caused the 2009 H1N1 pandemic. This pandemic A (H1N1) 2009 virus has been widely circulating across the globe since 2009, and is now established in human populations as

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a seasonal influenza virus. We know neither when a new influenza pandemic might start, nor where it will begin or how severe it will be.

However, we certainly know that we need to be prepared.

Preparedness, prevention, and control measures have all been implemented successfully during previous epidemics.

They must be implemented during 4 phases: • Pre-epidemic preparedness • Alert: identify, investigate, evaluate risk

The most notorious pandemic for which data is available is the “Spanish Flu” in 19181919, which caused an estimated 20-50 million deaths worlwide.

• Outbreak response and containment operation • Post-epidemic evaluation.

The process of global disease surveillance involves the systematic collection and collation of information, including rumours, from many different sources, such as government ministries, other United Nations organizations, nongovernmental organizations, the Internet, mass media and personal communications. Then, the lessons learned from the epidemics and pandemics of Ebola, Zika, pandemic influenza, yellow fever and cholera showed

that it is crucial to rapidly characterize pathogens, assess their virulence and clinical severity; protect health care workers, thereby protecting the investment in the health system; expand partnerships so that disease-fighting efforts are better coordinated and more effective during the next epidemic or pandemic and finally maintain global stockpiles of vaccine and/or treatments to ensure timely and equitable access to lifesaving interventions (WHO).

We mustn’t forget, particularly regarding the current global political situation, the threat of bioterrorism. The use of microorganisms as a weapon always appeared appealing to the warfare, although it is thought that the difficulty of manipulation and the unpredictability of these agents have kept this potential hazard at bay.Nevertheless, nowadays, with the development of the scientific field on biotechnology and genetic engineering, this might well become the most prominent reality of terror campaign.

Transmissible diseases didn’t get out of style with our development and evolution, remaining a leading cause of mortality and morbidity, especially in developing countries. Even the developed countries are now victims of their own progress, with the emergence of resistant microorganism and bioterrorism. There is still work to do in this area, being paramount to invest in novel technologies, systems, and techniques validated and adapted for disease intervention and control. The existence of a plan to face a possible epidemic or pandemic challenge mustn’t restrain the motivation to look forward for better approaches. In this eternal battle for the species survival and ecosystem balance, the bug won’t stop mutating. And neither should we.

Professor Parveen Kumar A determined woman, a caring doctor and a passionate teacher

AUTHOR

Keynote Speaker

Catarina Nunes

Professor Parveen Kumar is an outstanding woman and professional. Truly passionate about her job, Professor Kumar qualified at St Bartholomew’s Medical College London and is a gastroenterologist, besides teaching at Barts and the London School of Medicine and Dentistry. In addition, she is also the co-founder and editor of “Kumar and Clark’s Clinical Medicine” and started the first gastroenterology MSc (Master of Science) course in the UK.

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n 1999, she became the first recipient of the Asian Woman of the Year award, and in 2000 was made a Commander of the Order of the British Empire in recognition of her services to medicine, which had also given her the British Medical Association’s Gold Medal.

Professor Kumar made her way into Medicine in a time where women didn’t quite have a place in universities and there were quite a few women working in this field. However, becoming a doctor was a dream for as far as Professor Kumar can remember. Why Medicine?

Because it combines two things she valued the most: being a scientific field and being a caring profession. “You cannot ask for a better job.”

And so she became a doctor, a researcher and a teacher with a desire to make the difference, her greatest ambition.

One of Professor Kumar’s biggest passions is teaching. She believes that medical students help her feel young, keep her up to date and that she can learn a lot with them. “Students ask the most penetrating questions”, she says. Professor Kumar also wrote an outstanding book along with her teacher and mentor Professor Clark that every medical student should read: “Kumar and Clark’s Clinical Medicine”.

When asked about the reason why she decided to write it, she says “I wanted to write an interesting book with lots of pictures and colours that turned it into something fun to read. Because if you’re

«making the difference is something to be done everyday and a neverending mission.» not having fun, something is not right!”

Teaching is something justly valuable and a good education is what will make the difference for what’s to come.

When one listens to her speaking, it is impossible to miss out her determination and her enthusiastic personality. Kumar is, as she doesn’t cease to say, lots of fun. She believes one of the most important aptitudes for a doctor nowadays is to be able to be part of a team and work as one.

On how to be a great doctor, Professor Kumar says: work hard and have fun.

Medicine is a hard path to choose. If we are not having fun, then it is not worth it. Another important aspect is to never be arrogant. Arrogance will lead you to a path you do not chose and get you away from where you want to be. And last but not least, give the best to your patient.

That is what truly matters: the lives of the ones who come to us for help. That is the most valuable treasure we have and it is a doctor’s obligation to preserve it.

Professor Parveen Kumar is, above everything, an inspiration for us all.

Her greatest ambition to make the difference is, I believe we can say this, accomplished. However, making the difference is something to be done everyday and a never-ending mission.

Professor Kumar shall remain a determined woman, a caring doctor and a passionate teacher, besides being an outstanding human being to whom the Scientific and Medical Community will always ow the most sincere “Thank You”.

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cutting edge

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The history of surgery AUTHOR

Miguel Antunes

T

o talk about the history of surgery is to necessarily talk about the history of medicine and, therefore, the history of humanity.

Being that so, and even though it is not my intent to bring the reader back to its elementary school history lessons, I find that this is a rather interesting effort, and most of all, a necessary one.

It was the 16th Century, Pedro Álvares Cabral was finding Brazil, Leonardo Da Vinci was painting the Mona Lisa and Ambroise Paré was being born. The latter was to become one of the fathers of the art surgery and of the art of shaving.

Curious, isn’t it? In the eyes of today’s society a man with a razor and a man with a scalpel are in opposing extremes of the work force. However, in the year 1500 the scalpel was still to be invented, and so there was the surgeon-barber, a man whose razor had to service both jobs: to treat the beard and the bullet wounds.

Paré, an outstanding man for his time, stated that to perform a surgery was ‘’to eliminate that which is superfluous, restore that which has been dislocated, separate that which has been united, join that which has been divided and repair the defects of nature.’’. This is a rather holistic vision for a time when asepsis and anaesthesia were mere dreams and dissections had just become a legal practice in the eyes of the Church.

It is interesting to think that since Galen in Ancient Greece all the way to the 19th Century there were little advances in surgery. There were some improvements in terms of tools and such but the big improvements, the ones that drastically impacted the mortality and morbidity only came with great technological advances, later in the 20th century.

«To talk about the history of surgery is to necessarily talk about the history of medicine and, therefore, the history of humanity.»

It may pain us to hear this, however, we must all be aware that up until the late 1970´s many women with a suspected malignant nodule in their breast were subjected to a procedure called a radical mastectomy. It consisted in the removal of the breast, the axillary nodules and both the pectoralis minor and major muscles. This surgical approach, which was highly incapacitating for women, was foreseen as an unquestionable one, and many of the surgeons who tried a more conservative way of therapy were labelled as cowards and incompetent.

This procedure that can nowadays be considered barbaric was common practice in the United States just 40

years ago.

As you can see, a lot has changed in little time, but it is my belief that today Surgery is necessarily a product of all its history, the ancient and the modern.

Ultimately we are not only talking about an area of science, but rather an art form, which is in itself as old as humanity but extremely young simultaneously. This form of art has been confronted in recent years with a lot of new challenges and has been forced to evolve due to an immense amount of technology and information being introduced. This has caused a shift in paradigm.

In today’s operating room the surgeon is no longer a solitary figure that concentrates in himself all the knowledge and the decision power, but rather one of the many intervenients that aid in the improvement of a patient.

Surgery has become highly dependent in other areas of medicine, but it hasn’t really lost the near mystical touch that it had throughout the ages. Being a surgeon still encaptures, perhaps now more than ever, the beauty of mixing the audacity of Álvares Cabral, the craft of Da Vinci, and the willingness to help others that is inherent to the medical profession, and that was present in Ambroise Paré and many different figures that helped shape this phenomenal area of medicine throughout the ages.

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Can robots turn into surgeons?

AUTHOR Cláudia Silva

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few decades ago, this was probably impossible. However, there’s a different answer now and it’s called “Robotic Surgery”, as it seems that robots have arrived to the operating room and are here to stay. The word “robot” is derived from the Czech word “robota” and means forced work. It was in Vancouver, in 1983, that a robot was used for the first time ever, to assist in surgery.

Robotic Surgery can be defined as a type of surgery where a doctor manipulates a robot through a joystick, which makes the incisions and resections. Not only does it improve surgeons’ abilities in open surgeries, but it also reduces the impact on minimally invasive procedures. It almost works as an instrument inside the patient that the surgeon can control from the outside. That’s why this technique offers the possibility of operating at a distance, which is a great advantage. And I’m not talking about five or six meters separating the console and the operating table itself, but hundreds (or thousands) of kilometers. Just imagine a surgeon doing this procedure in his office and the patient in another corner of the world, on an operating theatre and assisted by a second surgeon. The only reason why this is not yet possible is the speed of internet connections (which does not allow immediate response times).

Robot-assisted surgeries depend ultimately on the hands-on ability of each surgeon, reflecting their experience and training, with diverse results. One of its main goals is to diminish the likelihood of complications, apart from promoting greater efficacy and safety. An essential information, considering that recent studies showed medical mistakes as the third-leading cause of patients’ death. Other benefits include: bigger precision, high definition image, improved dexterity, less incisions and less blood loss, in addition to faster healing.

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The patient’s recovery time is a lot shorter (they can leave the hospital right away) and there’s also a better manipulation and magnificent tridimensional moves, filtering out the casual tremor of the surgeon. However, there are some drawbacks and the main one may be: the high cost of the robot (over a million dollars), not to mention the additional training needed to use the equipment (although the learning curve is shorter than in laparoscopic surgery). Another disadvantage worth mentioning is the lack of sense of touch, increasing the risk of tissue damage.

Nowadays, da Vinci is one of the highlights in Robotic Surgery, being the most complex robotic system used in clinical practice.

According to history, it was created in the USA to allow military surgeons to remotely operate wounded soldiers in the Gulf War and applies the same technology used by NASA in its space missions. In 1995, da Vinci was developed by the American Company “Intuitive Surgical Inc”, being a promising invention and approved by the FDA in 2000. It has three components. The first one is the robot, a body with four articulated arms and 360-degree flexibility. A camera is coupled to one of its arms, revealing 3D images, while the other 3 arms manipulate the surgical instruments and reproduce, in a precise way, the surgeon’s hands-motion.

The second unit is the console, where the surgeon sits and performs, since the robot replicates his moves. The third unit incorporates an external console with monitor, where the surgeon’s assistants, positioned next to the patient, watch the surgery.

What’s interesting about this whole robotic scenario is the chance that a robot might even be more delicate than a human. But can robots replace surgeons?

It’s important not to forget that these robots are not autonomous and it’s always

essential that a surgeon operates and inputs instructions. Like Dr. Monique Spillman once said: “Surgery will always need the human touch”.

Currently, worldwide, more than two million patients have been operated with the help of robots (mostly in the USA, Spain, France and Belgium). Furthermore, also in Portugal, Robotic Surgery is a reality that has begun to gain shape. On June 23, 2010, an important milestone was reached: the very first robotic intervention in Portugal, at Hospital da Luz. It was a radical prostatectomy. Dr. Kris Maes, a Belgian urologist and an expert in Robotic Surgery, guest of the Hospital da Luz team, has already performed this surgical intervention a great number of times. Besides Urology, the da Vinci Si HD system has also been used in General Surgery (for example, in bariatric and colorectal surgery). In Portugal, three centers have this equipment: Hospital da Luz, Hospital CUF Infante Santo and Champalimaud Foundation. Because of their movement versatility, robots can avoid touching nerves when removing a cancer of the prostate or the rectum and its accuracy can guarantee the maintenance of functions such as continence (urinary and fecal) and male sexual potency.

Robotic Surgery still has some obstacles to overpass, but there’s no doubt that the future of this alliance between medicine and technology will be revolutionary and full of surprises. After all, maybe robots are the next heroes of our time, where machines become the extension of the surgeon’s hands, which command the robot as a maestro coordinates an orchestra. That being said, a final question stands out: Would you mind if a robot performed your surgery?

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Face transplant: a real solution or a deviation from the real problem?

AUTHOR

Mafalda Jorge

T

he ethical debate around face transplant has been one-sided and sensationalist. Under the influence of some science-fiction movies, where the intervention is used for nefarious or vanity purposes, many people still look at face transplant as an outrageous procedure in which people are “using someone else’s face”. However, besides being an outlandish concept with scifi connotations, face transplant is beginning to be accepted as a feasible and relevant treatment for many disfigured patients who have been marginalised by society their whole lives. So, what are exactly the benefits and risks of face transplant? Is it the best solution for disfigured patients?

In the first place, commonly known as facial transplantation, facial skin allograft (FAT) is an example of composite tissue allografts, which are transplants of organs composed of multiple tissue types that express different degrees of antigenicity. FAT for reconstruction of severe facial deformity is not a cosmetic procedure or a facial identity swap, but rather a lifesaving opportunity for the suffering of individuals with severe facial deformities. It is imperative to note that the face is an organ of expressivity, not just a static mask, which provides a range of emotions and feelings, evidently important in an effective communication. Disfigured individuals, unfortunately, are not able to reveal as much as they could

with their faces because our society can’t deal with their deformities and, therefore, rejects them by judging their different appearance, effectively ostracizing them and avoiding any kind of social interaction with them.

«[...] reconstruction of severe facial deformity is not a cosmetic procedure or a facial identity swap, but rather a lifesaving opportunity for the suffering of individuals with severe facial deformities.»

In this order of thinking, we should take all the advantages and disadvantages of this technique into account, so that our preconceptions and social attitudes don’t trivialise the suffering of these individuals and their right to choose experimental procedures to improve their situation.

Thus, it is necessary to know the new ethical questions that are arising and to be a part of the actual controversial debate of facial transplantation.

So far, about 30 facial transplants have been performed worldwide. A few years ago, one of the main concerns focused on the idea of “wearing someone else’s face”. Throughout the years, it was

demonstrated that facial transplant recipients gain a new appearance that is different from the recipient’s and the donor’s face. However, nowadays, new ethical problems are arising. Many specialists still claim that it is not a lifesustaining organ transplant and that the potential side effects are too great to justify the operation. The most common issues debated are related to the need for lifelong immunosuppressive drugs, to the importance of identity change and psychological effects and to the quality-of-life issue.

«However, nowadays, new ethical problems are arising. Many specialists still claim that it is not a life-sustaining organ transplant and that the potential side effects are too great to justify the operation.»

One of the main questions is whether improving quality of life can justify the risks of immunosuppression. As stated before, the procedure is a composite tissue transplant that consists of connecting small nerve and blood vessels through microsurgery. The biggest hurdle is that the recipient’s body rejects the new face. So, to

AIMS Specialressonância Edition • 15 • 15

avoid rejection, the patients need to take drugs to suppress their immune systems. In the long term, these drugs can lead to cancer, infection or liver and kidney failure. On the other hand, the immunosuppressant drug can also fail and, in this case, the face might have to be removed. When the patient no longer needs to take those medications the facial transplant becomes a reality. Thus, the risk-benefit balance is critical in this situation.

«the procedure is a composite tissue transplant that consists of connecting small nerve and blood vessels through microsurgery.»

Regarding psychological effects, from the perspective of the donor’s family members, it might be difficult for them to adjust seeing their relative’s face on another person, even if the recipient doesn’t look exactly like the donor.

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Besides, from the perspective of the recipient, it might also lead to identity problems if he finds difficulties in accepting his new face as his own. We should not forget that this procedure, despite requiring a precise surgery, also carries a great emotional load and real psychological questions.

Taking into account the above mentioned risks, it is necessary to determine if the transplant will improve the person’s life by improving his facial appearance. Although face transplants will not save anyone’s life, it might enable some people to improve their quality of life. Some disfigured individuals struggle with depression and isolation and are not able to recover psychologically and to overcome their past. Their faces still remind them of what they have been through and, moreover, our society is not able to accept them and support their needs.

Yes, it would be better to see an effort in helping these individuals re-entering society. Yes, it would probably be better if they had not to be submitted to a face transplant. However, until society can look beyond the face of deformity and see the face that reveals the patient’s inner worth and dignity, the

need for facial transplant will remain.

To sum up, all the questions previously discussed belong in today’s field of facial transplantation and must be further analysed with the purpose of exploring this field to its maximum potential in a safe and ethical manner. Advances in immunomodulatory and immunosuppressive protocols, computer-aided surgical planning and microsurgical techniques have enabled broader clinical application of this procedure to patients. Consequently, it is turning into a real solution for disfigured patients.

However, we should never forget something… if society could accept them as “normal people”, would these individuals ever be submitted to social discrimination? If we could welcome them in our society, without ostracizing them, would it ever exist the need for a face transplant? If we could just look beyond, would they ever notice that they needed to change?

So, here is my question: is face transplant a real solution or a deviation from the real problem?

The bionic eye AUTHOR Ana Lúcia Fernandes

I

t was the year of 1929 when the first idea of vision beyond blindness was born from a german neurologist called Foerster. He concluded that phosphenes, a light sensation in the absence of visible radiation (e.g. when we press our eyeballs through our closed eyelids), could arise from electric stimulation of the occipital pole of the brain.

The confirmation of the lingering function of the visual cortex after deprivation of visual stimulation would breed attempts to recover the lost vision.

Graham Tassicker succeeded in deepening this idea by patenting a prosthetic device, in 1956, which expressed how a photo-sensitive selenium cell located behind the retina culminated in phosphenes on a blind patient. It was then 2011 when the first retinal prosthesis, Argus II, manufactured by an American company, received CE (Conformité Européenne), accomplishment succeeded in 2013 by the FDA (Food and Drug Administration - US) approval under a humanitarian device exception.

To set our imaginations low, it’s more clarifying to refer to the bionic eye as a retinal prosthesis. This prosthesis aims to restore the basic visual function of blind individuals, mostly motion detection and object localization, by electrical stimulation of neurons in the visual pathway. It replaces photoreceptor properties by evoking ganglion cells of the inner retina response that activates, through the optic nerve, the subcortical and cortical visual areas, which, in turn, induce a phosphene.

Nonetheless, this pathway coerces the resolution of blindness subsequent to injuries that affect ganglion cells or the visual pathway downstream, like glaucoma and severe trauma involving both eyes, making treatments with bionic eye recommended only for outer retinal diseases, such as retinitis pigmentosa.

Currently, there are two different

prostheses with CE marking for the treatment of retinitis pigmentosa: the Argus II and the Alpha-IMS. The most obvious difference between them is the external camera utilized by the Argus II, rather than the employment of the subject’s own eye to capture the image onto a photovoltaic component, set by the Alpha-IMS. Focusing in the Argus II, the image from the external video camera is processed in real time into electric patterns, due to a small portable computer known as visual processing unit (VPU). These patterns activate the electrodes of the retinal prosthesis, managing to stimulate the residual inner retina. Though the external system seems uncomfortable, it allows an improvement of the image encoding. Trials have demonstrated that 58% of the patients with Argus II system on were able to navigate to a door, compared to the 32% with the system off. Moreover, in a closed set test 73% of the patients with the system on were able to identify letters, instead of the 17% with the system off.

al inner retina. The only problem was that this MPDA was unable to convert enough energy to reach the retina neurons threshold. This issue was settled with the introduction of retro-auricular coils that supply electric power via radio frequency telemetry. So, besides the MPDA and the coils, we have a silicone cable connecting them both.

To conclude, the next target is the improvement of the quality of vision within these treatments. Although it seems expensive and almost inaccessible, there are studies which show that Argus II is cost-effective compared to the traditional care of retinitis pigmentosa. Nevertheless, we can’t forget that this is a fixing method that doesn’t deal with the source of the disease.

Researches are being conducted towards the pith of the matter, for instance, with new approaches that include gene therapy, cell transplantation and cytokine therapy.

2.

2. Alpha-IMS system

References: •

1. Argus II system •

Focusing now on the Alpha-IMS, the photovoltaic component anteriorly referred stands in the form of a micro-photodiode array (MPDA) and converts electromagnetic light waves into electric current, activating the residu-

•

Ong, J. m., & Cruz, L. (2012). The bionic eye: a review. Clinical and Experimental Ophthalmology, 40: 6-17 Luo, Y. H., & Cruz, L. (2014). A review and update on the current status of retinal prostheses (bionic eye). British Medical Bulletin, 31-44 Vaidya et al (2014). The cost-effectiveness of the Argus II retinal prosthesis in Retinitis Pigmentosa patients. BMC ophthalmology, 14:49

AIMS Specialressonância Edition • 17 • 17

The Health Error Keynote Speaker AUTHOR Jorge Rebola

D

octors have always been portrayed as figures with higher powers, someone whose ability and activity is somehow based or supported in a dimension that is not common to other occupations.

Don’t misinterpret me. I am not making a presumptous assumption of the superiorness of medicine over any other kind of science, art or profession (even though the simple fact that I am comparing it to these three distinct categories migh betray me...).

It is rather a conclusion from the way Doctors are pictured culturally in traditional societies. People trust their lives on us (That’s right. Us. We better get used to it). Without having any previous connections. We are not friends, we are not family, we are merely someone they have met recently, talked to a couple of times and yet they trust themselves on us. Ok, I admit it is a reductive perspective but still the best way to deconstruct this odd relationship and infer the empowerment it gives us, the position we stand in and ultimately the responsability it represents.

On the other hand, this pedestal in which Doctors are put is not often questioned by themselves (Notice I’m not saying they souldn’t be there...). But who can blame? As a matter of fact who doesn’t like to be highly considered?

(Don’t lie to yourself...).

I am not simply suggesting Doctors are so blinded by their ego they deny reviewing their condition. It’s rather unconsciously assuming the role they are conceptualized to fit in and be faithful to it with everything that comes along with it. And again, this is seldom a synonym of a neglectful overbearing conduct. No. It’s quite the opposite actually. Incorporating this

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role makes Doctors push themselves to the limit. They demand only the most and the best from themselves, setting a dangerously high bar. No space for carelessness, no space for oversight, no space for flaws, no space for errors.

And here lies the core of this question.

Doctors are not allowed to commit any error. And they don’t allow themselves to. Doctor José Fragata has dedicated part of his life studying this matter – medical error, or as he prefers to call it “health error” due to the fact that the Doctor is by no means the only intervenient in this question. As the time goes by, this is becoming an urgent matter to be considered and worked on.

Not only is it becoming preponderant but it is something very unconsidered and ignored by the medical community.

It is a huge elephant in the room. As a matter of fact, studies from John Hopkins university point medical error as the third leading cause of death in the USA, surpassed only by oncologic and cardiovascular diseases. And yet, the error in medicine is still some obscure concept better swept under the rug. But this paradigm has to change.

Errors are an inevitability of the human being’s imperfection, they are directly linked to his nature. It can no longer

be a taboo and must be dealt from the inside.

A Doctor cannot hide a error he has comitted for being afraid of seeing his work being discredited by colleagues, being ruled out or losing authority or respect. We must create the conditions so that anyone can indiscriminately report an error without fear of reprisals.

As Doctor Fragata says “informing is an ethical obligation of physicians and satisfies the autonomy right of the patient”. This sense of fallibility must be reckoned without prejudice. “It is essential that physicians have the notion they are not infallible” sums up Doctor Fragata. It seems like a doctor can’t be fallible but yet he is. He must be. He’s human.

on the battlefront

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Russian Roulette AUTHOR

Nuno Fernandes

“It is likely that unlikely things should happen.”

Aristoteles Despite all the fallacies of any oversimplification, cancer can be boiled down to a set of mutations in a cells’ DNA. As our cells divide, the accumulate several mutations which are passed down to the subsequent generations of cells; some mutations result from the random errors of the DNApolymerase machinery or faults in the DNA repair and proofreading systems (intrinsic factors), but they can also result from carcinogens and mutagens present in some hazardous materials (extrinsic factors).

In general, the DNApolymease system makes a mistake for every 10^7 nucleotides added. Proofreading and the DNA repair system decrease the error rate to one mistake for every 10^9 nucleotides added. However, this error rate is increased in people with mutations in genes responsible for the polymerases or the DNA repair system. Mutations that alter proteins that regulate the cell cycle and growth factors or growth factor receptor can also be involved in diminish apoptosis, excessive proliferation and unchecked cellular growth, all of which play a part in cancer formation and development: Li–Fraumeni syndrome is caused by a mutation in the p53 gene, which encodes the p53 protein, a protein that is responsible for halting the cell cycle and inducing DNA repair mechanism when DNA errors are detected; BRCA1 and BRCA2 are DNA repair proteins; Peutz–Jeghers syndrome

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is caused by a mutation in LKB1, a tumor suppression gene. Mutations in numerous genes, such as the ones aforementioned, have been associated to a higher rate of cancer. In addition, numerous carcinogens, present for instance in cigarette smoke, have the ability to either induce mutations or disrupt the DNA repair system.

Several studies have assessed which is the determinant factor of cancer: random mutations or lifestyle choices. A Science article (10.1126/ science.1260825) concluded that most types of cancer, such as pancreatic, leukemia, bone, testicular, ovarian and brain cancer, were due to random mutations, i.e. bad luck, rather than risky lifestyle choices. However, a later Nature study (10.1038/nature16166), pointed out some flaws of the “bad luck” hypothesis and concluded that the intrinsic factors only contribute less than 10-30% to the development of most cancers and that 70-90% of cancers were caused by extrinsic factors such as smoking drinking or UV exposure.

One of the authors of that study compared the risk of getting cancer with that of playing Russian Roulette.

There are 8 slots and at first there is only one bullet in one of the slots, which would equate to a risk of getting cancer of around 1 in 8. By smoking or being exposed to certain cancer-prone substances, people are adding extra

bullets to the revolver, increasing the chances of developing cancer.

That is what epidemiologist refer to as ‘attributed risk’. There is always a baseline risk of getting cancer, i. e. the 1st bullet, which is determined by our genetic background and pre-existing mutations (for example, mutations in the BRCA genes increase this baseline risk), and there is an added or acquired risk, the extra bullets, derived from the extrinsic risk factors. And from that point forward it is pure luck.

The percentage of risk attributed to extrinsic factors for each type of cancer varies, being some types of cancer almost purely ‘bad luck’ and other types of cancer being determined largely by environmental factors, such as smoking or air pollution. The problem with this game of probabilities is that no-one can ever be sure of which cigarette gave them cancer or even if any cigarette was the cause of their cancer, but what we know is this: putting toxins in our body will increase the chances of us getting sick. Smoking is never a guarantee of cancer and not every smoker gets cancer, but the chances of a smoker getting lung cancer are much higher than that of a non-smoker. In this game of chance, no-one can be sure of anything. The most we can strive for is that the odds be in our favor.

CRISPR, a New Dawn for Genetics?

AUTHOR

João Bastos A powerful gene-editing technology is the biggest breakthrough to hit biology since PCR. But with its enormous potential, pressing concerns arise.

Genetic Engineering has undoubtedly come a tremendous way since it first surfaced in scientific literature back in the 70’s. In these past few decades, we have witnessed the birth of extraordinary gene-editing technologies. In 1995, meganucleases (probably one of the most specific group of endogenous restriction enzymes) became the center of everyone’s attention after demonstrating their ability to meddle with mice genome. Zinc Finger Nucleases (first applied as a “technology” also in the 90’s) continue to this day being used, though with a cost of 5000€ or more to order, they were never widely adopted.

Finally, in 2007, having the ability to mimic eukaryotic transcription factors, TALLEN’s followed in the arc of promising, revolutionary gene-editing technologies.

Since the discovery of CRISPR as a gene editing technology in 2012, however, a new era seems to be approaching. With a cost of as little as 30€, scientists can now edit genomes with a precision, efficiency and flexibility unlike anything ever before.

Even more, with CRISPR, it’s theoretically possible to modify the genomes of virtually any animal, including humans.

Are we prepared to take the next leap?

The CRISPR/Cas9 System (often

shortened to just CRISPR) is actually a naturally-occurring mechanism found in a variety of bacteria. Back in 80’s, scientists observed a strange DNA sequence that repeated over and over again with unique sequences in between the repeats. They called this odd region “clustered regularly interspaced short palindromic repeats,” or CRISPR. It was only in 2005 that Francisco Mojica, from the University of Alicante, Spain, found that the unique sequences matched the genomes of bacteriophages. The defense mechanism

«With a cost of as little as 30€, scientists can now edit genomes with a precision, efficiency and flexibility unlike anything ever before.» relies on a group of enzymes called Cas (CRISPR-associated) which precisely recognize and inactivate genetic material of invading viruses, preventing them from replicating. There are lots of Cas enzymes, but the best known is Cas9, found in our beloved Streptococcus pyogenes. In 2012, scientists proved that simply by changing

the sequence of the RNA that Cas9 carried, they could reprogram it to target a specific site. A revolution in the way we explore the field of genetics was triggered.

The potential of CRISPR in developing a deeper understanding of gene function by knockout and knockin experiments is now evidently clear. Even more, the idea that CRISPR could accelerate the genetherapy field is becoming a major source of excitement in Medicine. The first trials will probably be scenarios in which the CRISPR component can be injected directly into the tissues. For example, hematopoietic stem cells might be corrected to treat diseases such as sicklecell disease or β-thalassaemia. Other great source of enthusiasm comes from the possibility of CRISPR finally being able to cure the dreadful HIV. Similarly, to other retroviruses, the genetic material of HIV wedges itself into the genome of its host. And while antiretroviral therapies are effective at repressing HIV, they don’t have the ability to eliminate the integrated virus, which can lie low in a latent state. With the discovery of CRISPR, however, we might have changed how the game is played. Researchers, led by Kamel Khalili

AIMS Special Edition • 21 ressonância • 21

at Temple University in Philadelphia, Pennsylvania, used the CRISPR/Cas9 genome-editing system to excise HIV from several human cell lines, including microglia and T cells. Khalili tells us: “It was a little bit…mind-boggling how this system really can identify a single copy of the virus in a chromosome, which is highly packed DNA, and exactly cleave that region.” His team proved that Cas9 could actually excise more than one copy of the HIV genome, having thus the ability to completely clean up the viral DNA in a cell. One limitation of the CRISPR/Cas9 approach is that it can chop up unintended regions of the genome, producing off-target effects. Khalili’s group performed whole-genome sequencing but didn’t find any off-target effects. T.J. Cradick, the director of the protein engineering core facility at Georgia Tech, said that a more thorough analysis of potential off-target effects might still be required to make sure nothing has been overlooked. Nonetheless, “latent HIV provirus is a very exciting target and… a very promising way forward,” said Cradick. The challenge to any kind of CRISPR approach remains the delivery as it may be very difficult to administer a genome editing-based therapy to a significant percentage of infected cells. Though the technology looks promising, a successful delivery strategy is imperious. Khalili has

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now set his sights on this particular challenge. His group is currently working to develop a nanoparticle delivery vehicle, and he hopes to be able to test it in a mouse model soon.

Despite the fascinating data, many scientists caution that there is a lot to do before CRISPR can be deployed safely and efficiently. Scientists need to increase the efficiency of editing but at the same time make sure that changes elsewhere in the genome are not introduced. Keith Joung, who studies gene editing at Massachusetts General Hospital in Boston, has been developing methods to track Cas9’s off-target cuts. According to his work, the frequency of these off-target effects varies widely from cell to cell and from one sequence to another: his lab and others have seen off-target sites with mutation frequencies ranging from 0.1% to more than 60%. Finally, the CRISPR technology has sparked brand new debate over genetic editing Human embryos. In a world first, Chinese scientists have reported that they used this technique to modify human embryos. Although the research group only used non-viable embryos obtained from fertility clinics, some scientists think that this kind of work should be well thought as it could be easily a slippery slope towards unsafe, unethical and non-medical use.

Some researchers see lessons for CRISPR

in the arc of other new technologies that prompted great excitement, concern and then disappointment in the history of science. Others are concerned about the ethical questions involved in the use of CRISPR in Human Beings. However, with the ability to easily tweak DNA, scientists can now theoretically remove genetic mutations that are responsible for incurable diseases, such as cystic fibrosis, HIV infection, and even certain cancers. Has a new dawn in the field of genetic therapy finally arrived? And are we, as a society, prepared to take this technology to the next level?

References: •

• •

• •

Sorek, Rotem, Victor Kunin, and Philip Hugenholtz. “CRISPR—a widespread system that provides acquired resistance against phages in bacteria and archaea.” Nature Reviews Microbiology 6.3 (2008): 181-186.

Ledford, Heidi. “CRISPR, the disruptor.” Nature 522.7554 (2015): 20.

Ebina, Hirotaka, et al. “Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus.” Scientific reports 3 (2013): 2510.

Cyranoski, David, and Sara Reardon.

“Embryo editing sparks epic debate.”

Nature 520.7549 (2015).

Fu, Yanfang, et al. “High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells.”

Nature biotechnology 31.9 (2013): 822-826.

Interview

Bruno Costa-Silva From his luminous office, filled with posters from his last address, New York, lined with pictures from his hometown in Brazil, Bruno Costa-Silva coordinates the youngest investigation group in the Champalimaud Foundation – the Systems Oncology Group.

The incredible laboratory space, with a wonderful riversight, displays the youth of the group, formed less than a year ago. New machines, arriving each day, complete the still empty spaces and the progressive growth is notorious. Furthermore, it is also evident the willingness to progress with new projects in an atmosphere full of openness and enthusiasm, strongly enabled by the team leader, Bruno Costa-Silva.

ressonância • 23

Interviewers: Catarina Relvas, Pedro Félix Photography: Catarina Alves Vale RESSONÂNCIA (R): Presently, you are the group leader of the Systems Oncology Group, at the Champalimaud Foundation.

When did your dream to become a scientist arise?

BRUNO COSTA-SILVA (BCS): I have always been that sort of annoying child in the “why” phase, which extended way beyond the expected length, and continued throughout my life.

Initially, I aspired to apply to a medical school. However, for numerous reasons – including the direct contact with the patients – I ended up enrolling in a Pharmacy degree, which still provided contact with the Health field, but in a more indirect manner.

In my first semester in college, I didn’t know yet I could join a laboratory and start working. Briefly after my enrollment, the Universities in my country went on strike, everything was closed and there were no lectures. I had studied so hard, and now the faculty was not open. Amidst that I thought, ‘I will not stay idle at home; I am going to make something out of this nothing and I am going to the laboratory’.

My Molecular Biology Professor had his own laboratory, and I started to work with him in a Scientific Initiation programme.

For the first time in my life, I felt the people there were as weird as I was – which was great! I had always been that nerd others found odd, but there everyone had the same interests and conversations as I had.

I thought that entering the Science world would be much harder that it actually was.

In reality, I felt very comfortable when I arrived.

R: You were born in Florianópolis, Brazil, where you concluded your baccalaureate in Pharmacy and Biochemistry. How did the opportunity to work abroad come up?

BCS: I became addicted to challenges. I started to feel a little too comfortable in Florianópolis, and at that time I wanted a new challenge and to go to Philadelphia, actually. I ended up not getting that

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position - I had not even understood the selection method - and the opportunity to work in the Ludwig Institute for Cancer Research in São Paulo came up. There I met Dr. David Lyden, with whom I collaborated and who eventually invited me to work with him, in Manhattan.

In his laboratory - at the Weill Cornell Medical College - I worked like an animal, and finished my postdoc. Until then, I had at least some emotional support: when in doubt over my experiments, I could resort to the guidance of my mentor. During the postdoc, I was for the first time treated like a doctor, I was expected to figure out things by myself - it was tough. However, from the moment I started to visualize the difficulties as opportunities, everything began to advance, and the results came.

I had 3 papers published in Nature, in 3 years. That’s something I had not even dreamt of getting.

In January 2015, the Champalimaud Foundation was beginning to recruit for the Oncology Group, Dr. David Lyden was a consultant to the Foundation and they wanted someone to work on Dr. David Lyden’s model here. They invited me to come to Lisbon for the interview and although I had already the contract closed to return to São Paulo, the proposal was so appealing, for me and my family, that I accepted.

R: Was there a mentor in your route, that had a particularly relevant impact in your choices and in the way you work today?

BCS: By crooked lines, David had a great impact on me. He was someone involved in many different projects and activities and I knew I could only approach him if I was facing a really difficult problem. His approach was to throw me to the wolves and it was tough. I knew I could only rely on myself. But in the end, it worked for me and I remember that period as a truly positive experience.

Here I try to have a less drastic approach, but for me it is important that the people working here have autonomy, especially the more experienced ones. Autonomy is something really important because people need to create and I can not be

the only creative brain in the lab. I must use the intelligence of the people working with me in my favor. I don’t see these people as working hands.

People are afraid of freedom, they think that exclusively the things written in books are the correct ones. Actually, if you are not capable of making free questions, you will become merely incremental.

The greatest ideas and discoveries are exercises of freedom.

«The greatest ideas and discoveries are exercises of freedom.»

R: Within so many possible fields of research, what excited you the most in cancer research?

BCS: Until I started working at Ludwig Institute for Cancer Research, in São Paulo, my field of research was Developmental Biology, studying microenvironment.

The process of transitioning to Oncology was an easy one, for the study of the tumor microenvironment has various similarities with what I was studying previously.

Cancer is a disease that makes us feel as if we were still in the medieval era and we are losing the battle because we do not understand it. I find that very scientifically stimulating.

There are too many people dying of cancer.

In my close family there were several cases of this disease and if we look around, many people we know also have it. That is relevant to me.

R: You have been living in Lisbon for almost a year, working at the Champalimaud Foundation. What is your average day like at the foundation?

BCS: This is my first experience as a group leader. I had mentored other people in the past, but being group manager is a totally different experience. I continue to produce scientific knowledge, and a kind

of science I truly appreciate, but nowadays I have to find excuses to walk around in the building, because most of my time is dedicated to writing and working isolated in my office. In addition to the time spent by myself, I keep working on the collaboration with Manhattan and with David, who is my consultant here, I have interaction with the clinic and give guidance to the people working with me.

The atmosphere of Lisbon is quite different from the one in Manhattan. Whether inside or outside the lab, the mood

in Manhattan was very harsh and aggressive. Here, the surroundings of

the city are different. The atmosphere of the foundation feels different. So far, I feel great freedom coming from my superiors.

There is a great interface with the clinic, something that pleases me a lot, and a great desire on the part of the foundation’s medical doctors to collaborate on projects.

R: What is the main theme of investigation the group pursuits at the present moment?

BCS: For now, the main theme of our investigation is the detection of premetastatic niches in patients. In fact, I am working on the detection of the premetastatic niche and, in parallel, I am heavily investing in the investigation of the metastatic niche.

Regarding the detection of the premetastatic niche, we are working with some other research groups from the foundation and with a french group to find radiological patterns to detect the modifications that occur using the mouse model, and then test whether the same modifications exist in cancer patients.

We are collecting blood samples from patients with different tumors at different stages that we will follow over the years, evaluating the evolution of the disease, in order to learn which markers are predictors and may allow early diagnosis, for example. In regards to the metastatic niche, there are some similarities with this work, but with a somewhat different scenario.

With this same interest, we are also working on what we call the more

detailed liquid biopsies, looking not only for messages derived from the tumor but also for messages from organs that are compatible with the formation of metastatic niches, by analyzing plasmatic stromal exosomes.

If we want to treat the pre-metastatic niche, the first thing we have to do is to be able to detect it. That’s what we’re working on.

R: What is your process of coming up with new ideas to research projects?

BCS: A few of the ideas we’re developing right now are drawer ideas, in which I started working when I was in Manhattan, using the freedom I had at the time.

Some ideas come up in lectures when, to explain something to someone, you approach the problem from a different angle. Other ideas develop during discussions with colleagues. For example, one of the subjects that interests me most at the moment are the comorbidities in oncology, like cachexia, common in pancreatic cancer, or coagulopathy, cause of death in so many patients. It is important, to me, to understand what is causing the death of these people, and not only dedicate my time to a specific subject of investigation.

I really cherish the interaction with the medical doctors, because they are the ones that can reassure me the the clinical relevance of what I am studying.

Before presenting any ideas, I ask myself which are the areas in which I can make a difference. I do not want to compete with something well established: if a diagnosis is already made with 90% certainty, I have nothing to add to that dimension, so I choose another path.

R: What impact do you predict your investigation will have in the clinical practice in the future?

BCS: What kindles me the most at the moment is measuring the host’s biology.

In an example, detection of dysfunctions in the biology of the myocytes, allowing us to understand the mechanisms behind cachexia.

The ultimate goal in understanding the host’s biology is to treat the host as a whole - and not only the tumor - turning cancer into a chronic disease. People would start dying from other causes rather than from the cancer. Although, culturally, we are not ready to accept living with a tumoral mass all our lives, it can be, at least, an alternative.

Research over the last years, has been very much around the warlike approach to fight cancer. I find much effort is already being put in this way, thus I rather direct my efforts towards a more diplomatic approach. Before such, we ought to know the host better, so we can detect the disease earlier and even stractify it.

Farther into the future, evolution will allow us to find earlier lesions that are not perceivable through imaging methods.

That, combined with a vast knowledge of stroma, can grant a following without unnecessary surgical acts to remove the lesion.

R: Looking into the future, which do you predict will be the biggest changes in the field of cancer research and treatment?

BCS: With the increasing biomarkers discovery, the disease systemic approach is going to be what changes the most.

For instance, we will be looking at the bone marrow in a melanoma patient. We will focus not only in the tumor and its removal, but in the system as a whole.

One day, we are going to detect dormant tumors, and I hope that at that point in time we will have already accumulated enough knowledge to contextualize the result. Without this context, that isolated result can be very dangerous.

There are also ethical implications in this.

When we investigate new biomarkers, we need a control group, in which the individuals don’t have tumors. However, if we find in one of these individuals a tumoral biomarker, what should we tell that person? We have to find the answers to these questions.

AIMS Special Edition • 25 ressonância • 25

Translational Medicine Keynote Speaker AUTHOR

João Martins

T

he European Society for Translational Medicine defines it as an interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside and community. The goal of translational medicine is to combine disciplines, resources, expertise, and techniques within these pillars to promote enhancements in prevention, diagnosis, and therapies.

The European Society for Translational Medicine defines it as an interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside and community. The goal of translational medicine is to combine disciplines, resources, expertise, and techniques within these pillars to promote enhancements in prevention, diagnosis, and therapies.

Meet Dr. Sandra Swain, Professor of Medicine and Associate Dean for Research Development at Georgetown University Medical Center. Swain is an international reference in breast cancer, having published over 230 papers in peerreviewed journals. Her research interests

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include clinical trials and translational research in metastatic and inflammatory breast cancer, adjuvant therapy for breast cancer and health care disparities.

Swain first took an interest in Oncology during her Internal Medicine residency: “The patients were in dire need. They were sicker than most of the other patients.

And I liked the fact I was taking care of the whole person”. A prestigious Oncology fellowship in the NHI immediately followed. Nevertheless, after a couple of years in the lab, Swain realized that she missed working with patients, with real people: “For most physicians, the reason you go into medicine is to see the patients.

I liked the patient aspect of it and the connections with people”.

She eventually moved on to Lombardi Comprehensive Cancer Center at Georgetown University, where she started the breast cancer program. From then on, Swain has devoted her career to researching on breast cancer while helping oncologic patients herself, connecting the benchside with the bedside: “Much of my research has not been in the laboratory itself but using the patient as my laboratory”.

Among several other clinical trials, Swain conducted the CLEOPATRA study, a major breakthrough in the management of HER2-positive metastatic breast cancer.

She discovered that a certain combination of drugs could significantly increase median survival rate for this subset of

patients. It shifted the paradigm. On top of that, by putting her results into practice, Swain determinedly changed her own patients’ lives.

Additionally, Swain fondly values her position as a Professor at GUMC, recognizing the importance of education.

She says she wants to be a role model to her medical students, inspiring the next generation of researchers. Assuredly, she will.

Currently, Swain keeps on investigating promising targets for breast cancer treatment. According to her, curing breast cancer has been her lifelong goal.

Hopefully she will still make groundbreaking advancements in this field, bringing hope to thousands of patients.

Science is the root of today’s Medicine: in order to provide our patients with the best possible care, we must first have prime scientific evidence. We continuously build our practice on top of our knowledge.

What links them is translational medicine.

Let go of the idea that you must either be a physician or a researcher. You can be both.

Moreover, since you are able to apply your findings to your own patients, it’s a rather rewarding career path. You have the choice.

Don’t miss this opportunity to listen to Dr. Sandra Swain. Come find out what a physician-researcher actually is and learn what it takes to do translational medicine.

Remember science and what it’s for. You too can change the world.

cultural & charity program

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Cultural & Charity program AUTHOR

Catarina Nunes

“A

doctor that only knows about Medicine, not even about Medicine knows.”

A wise aphorism, don’t you think? Being a doctor is above all being a human being who contacts daily with so many different realities and people, that the emotional dimension of life simply cannot be left out. The AIMS Meeting believes that it is as important for a health student’s education the cultural and social wisdom as the scientific knowledge is. In this way, the 8th AIMS Meeting is, as previous editions were, proud to be offering every participant the chance to get to know better one of the most beautiful cities in Europe, the timeless Lisbon.

Known by its wonders worldwide, Lisbon is truly an adventure worth living. It is a city full of history and beautiful landscapes that you can appreciate with every step you take.

Once again, this year the participants

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will be able to take on this adventure to get to know Lisbon guided by Lisboa Autêntica. Lisboa Autêntica has prepared an unforgettable experience that will take you to Chiado, where the streets are filled with stores and

history; Lisbon’s downtown, where you can find art everywhere; Bairro Alto, where the lively steep streets will make you feel at home and Alfama, the place where the magical and melancholic Fado was born.

This year, the Cultural Program will also offer the participants the chance to visit one of the most iconic museums this city has to offer you: the Coleção Berardo Museum.

This museum is located in one of the best parts of town: Belém.

Full of history and with a beautiful view, don’t miss the chance to visit it! The participants will be able to visit the museum, which is known by its outstanding contemporary

collection. If you are a fan of modern art, then this is the place to go.

Another museum the 8th AIMS Meeting is proud to announce will be a part of the Cultural Program is the Calouste Gulbenkian Museum. Surrounded by an exquisite garden full of life, where you can take a break from the stressful outside life, the Calouste Gulbenkian Museum is famous for being a huge promotor of Art. The exposition

that you will be able to visit is called “José de Almada Negreiros: a way of being modern”. And the motto of this exposition is a famous quote from the author: “This thing of being modern is like being elegant: it is not a way of getting dressed, but a way of being. Being modern is not to do the modern calligraphy but to be the legitimate discoverer of the novelty.” Curious? Come visit it!

House of Fado

Another project the 8th AIMS Meeting is proud to ensure once again is the Charity Program. The Charity Program gives you the opportunity you’ve been waiting for to help others. The participants will have the chance to work at a Lisbon area volunteering institution for an evening. These are institutions that devote themselves to gathering and distributing food, visiting the homeless and speaking to those in need. You’ll get to be with them and help them do some of their work!

Re-food is an organization that aris-

es from the need to eliminate hunger in the local communities as well as the willingness to eliminate food wasting.

These volunteers develop a simple yet amazing work: they go around the local community collecting food from partners (like restaurants) to prevent it from being wasted and make sure it gets to the ones who real- ly need. If you’d like to help them, here’s your chance! You will have the opportunity to participate in one of their daily routes of collecting food.

Comunidade Vida e Paz and CASA are two amazing projects that aim

to help the homeless people living in the Lisbon area and will surely change the way you feel about volunteering. Day-by-day, these volunteers go meet these people in need and offer them food and clothes.

They also make sure these people know they have someone to talk to and try to provide solutions for their lives. Their role in these people’ lives is truly outstanding and notable.

The Conversa Amiga project is a truly outstanding charity project that is making the difference everyday among those who are in need.

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“Because when we talk, we are more human.” All these volunteers aim to fight is loneliness and isolation. They make sure everyone has someone to talk to, being an elder or a homeless person.

They are proof that small actions make big difference. Want to join them? Here’s your chance! Come join them on their “Um Sem-Abrigo, Um Amigo” project!

If you have always wanted to be there on the field, getting to know these different realities face-toface, here’s your chance. You don’t need to bring anything but yourself and the urge to make a difference!

The AIMS Meeting is also starting a new project: we are doing a campaign in favour of the Aldeias das Crianças SOS. Aldeias de Crianças SOS is a charity

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project that helps children worldwide.

These small families worldwide end up being the biggest family in the world and all they aim for is to protect children that are living in vulnerable environments. They are making a difference by giving them a home and a happy place where they can be in a supportive setting. So we want to challenge you to help them! Three days to change these children’s lives. You in? During the 8th AIMS Meeting we are challenging you to bring what you can from the list below: Food items that won’t spoil (olive oil, rice, pasta, etc.)

Hygiene products and home products (clothes and ware detergent, bleach, bathroom detergent, etc.)

Hygiene products like tooth paste, sham-

poo, shower gel and deodorants, etc.)

Remember: 3 days. Let’s make history.

Last but not least, the Gala Dinner will give you the chance to say goodbye to the best congress you will ever attend.

In this edition, the Gala Dinner will take place in Lisbon’s Oceanarium, a mytical and iconic place right next to the Tejo River. Need an opportunity to take that beautiful dress or that classy-chic smoking out of the closet?

The 8th AIMS Meeting Gala Dinner is the perfect time for that! Considered to be the largest indoor aquarium in Europe, the Lisbon Oceanarium is an absolutely historical place and has a stunning view. Don’t miss out on the chance to finish with style!

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SAV

NOVOS CURSOS

Guidelines 2015

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www.ocean-medical.com