Written in blood

Maltese researchers are leading the way in developing new diagnostic tools for cancer. Dawn Gillies finds out more from Prof. Godfrey Grech and Dr Shawn Baldacchino.

Breast cancer survival rates have been improving steadily in recent years. In Malta, 86.9% of patients currently survive, up 7% over the last decade. Thanks to new targeted therapies, the outlook is increasingly bright. But precision therapies need precision testing.  

Breast cancer diagnosis has reached new heights and with current tests using tissue biopsies, pathologists can classify patients for specific treatment. Precision medicine goes a step further. It provides more information, predicting the aggressiveness of the cancer and measuring the number of cells from the tumour that spread into the bloodstream. 

Dr Shawn Baldacchino

This does not mean that all requirements in precision therapy have been met. 

At the time of writing, there is no simple method to test patients’ ongoing benefit from treatment or to measure different tumour areas from one sample. For this to be possible, we need super-sensitive tests. This is where Prof. Godfrey Grech and Dr Shawn Baldacchino at the University of Malta come in.

Detecting the undetectable  

During his PhD, Baldacchino studied a new class of breast cancer representing most cases of the triple negative type, which affects 12% of breast cancer patients in Malta. 

In triple negative breast cancers, tests for estrogen receptors, progesterone receptors, and excess HER2 protein all result in negatives and are associated with aggressive tumours.  

To detect this new class of breast cancer, Grech’s team have created a new test that uses molecular substances we naturally produce in our body—biomarkers. By pinpointing the right combination of certain biomarkers, they can test for this new class within the triple negative breast cancer cases.

They initially used the test to look at biopsies from past patients. These exercises showed that they could accurately detect the cases—even in samples that were over a decade old! In fact, the test was so successful that the team is now working with biological testing industry giant Luminex to use it in hospitals worldwide. With a patent filed, research labs will get their hands on it later this year with the hope that by 2021 it will be used to directly help patients in hospitals. 

However, there is more work ahead. Encouraged by the results so far, the team wants to take the test and other current biomarker tests a step further. They want to use a simple blood sample which is less invasive, allowing patients to be monitored during therapy.

Pushing boundaries

With the method Grech and his team have optimised, obtaining information on new classes of patients that predict therapy use, detecting different tumour areas in one sample, and the use of blood to monitor the benefits of therapy have become a

Prof. Godfrey Grech, Dr Shawn Baldacchino and the team
Photo by James Moffett

possible reality. With technologies from Luminex and Thermo Fisher, they can now read over 40 biomarkers in one test simultaneously. But with blood they need a new angle. And that is happening through another test using particles that originate from cells called exosomes.

Exosomes are tiny messenger bubbles which cells release into the blood . ‘We believe that when there is a tumour in the patient, there will be a signature in these exosomes circulating in the blood,’ says Baldacchino. 

Finding these exosomes could mean detecting cancer at an earlier stage than is currently possible. The team believes they would be able to detect the exosomes that point to cancer long before a tumour shows up in scans and other regular tests—and so, they would be able to nip the cancer in the bud. But to do this, they need to be able to decode the messages the exosomes are carrying.

Positives for patients

It’s not only in the realm of breast cancer diagnosis and classification that the team can help patients—they might also be able to improve treatment. ‘Most targeted therapies currently try to inhibit specific receptors and proteins to stop the uncontrolled growth of cancer cells,’ Grech says. But through their research, the team has found that targeting the low activity of specific complexes of proteins in tumour cells is key. Their research models show that increasing the activity of these protein complexes is possible using specific drugs.  

This is true for triple negative breast cancer, where the amount of PP2A protein is extremely low. The PP2A protein enables the body to fight the cancer, so increasing its activity would create a chain reaction in the body which could limit the growth and spread of that category of cancer cells.

This approach to treatment has applications beyond triple negative breast cancer. Grech is hopeful that PP2A production could be amped up for different types of cancer too, and lead to positive results.

Managing the unmanageable

When organising a project like this, it’s expected that things won’t go to plan. One of the biggest challenges for Grech’s team has been establishing collaborations with other groups across the globe. They need these connections to provide the samples required to test their systems. With other groups working on similar projects, time is a limited resource. Thankfully, the team found collaborators in Leeds (UK), and Barcelona (Spain), allowing the group access to the samples they need. 

What is certain is that support for this work has come in many shapes and forms. The project received funding both from public donations and the Malta Council for Science and Technology. Baldacchino also found an ally in the charity foundation Alive with the help of the Research Trust of the University of Malta (RIDT). He is the first recipient of funding from them, and their first graduate.

Predicting the future

Thanks to projects like these, cancer research has a bright future in Malta. The team has their product launch to look forward to later this year, which will see a drastic reduction to the time and effort it takes researchers and doctors to determine the type of breast tumour.

But a lot of challenges lie ahead. The biggest challenge will come in the move to early stage cancers. These cancers have low levels of substances to detect, which means that any test they develop will have to be extremely sensitive in order to be effective. Successfully identifying these cancers would signal a massive breakthrough for the global medical community—and, more importantly, for patients. Early detection through basic blood tests would open the door to early stage treatment and a higher rate of survival. Nothing could matter more. 

Project ‘Accurate Cancer Screening Tests‘ financed by the Malta Council for Science & Technology through FUSION: The R&I Technology Development Programme 2016.

Talking Toys

While speech development starts early in life, the course of acquiring and processing language in a bilingual country like Malta is challenging. Engineers and language experts at the University of Malta have teamed up to build a toy that will help children overcome that hurdle. Words by Emanuel Balzan.

Toys and play are critical in children’s lives. It is through play that children learn how to interact with their environment and other people while developing their cognitive, speech, language, and physical skills. 

The way children play reveals many things including whether or not they are hitting particular development milestones. Play is also used by professionals who intervene when those skills are not acquired. Speech and language pathologists (SLP) use toys to tailor tasks based on their objectives for the child, determined following their assessment. For this reason, toys are vital tools. 

With technology moving at the rate it is, electronic components are easier and cheaper to access. As a result, a lot of smart, educational toys are now available on the market. However, Dr Ing. Philip Farrugia (Department of Industrial and Manufacturing Engineering, Faculty of Engineering, UM) honed in on a gap in the market—a smart toy that supports English and Maltese. 

Front left to right: Dr Ing. Owen Casha, Loridana Buttigieg, Emanuel Balzan, Dr Ing. Philip Farrugia, Prof. Helen Grech, Anthony Demanuele, Prof. Simon Fabri. Missing from the photo: Dr Daniela Gatt and James Attard.

To make this happen, Farrugia recruited a team of researchers from the university. Engineers Prof. Simon Fabri and Dr Owen Casha joined the effort. Researchers Prof. Helen Grech and Dr Daniela Gatt brought their expertise in speech and language acquisition and disorders. The team was finally complete when game development company Flying Squirrel Games stepped into the picture.

Getting down to business

The SPEECHIE project is divided into three stages. During the first phase, we sought to understand the process of speech and language acquisition, assessment, and therapy. We involved users through workshops that allowed us to observe children’s play and their toy preferences. We also conducted focus groups with parents to identify what they most wanted from toys. During these sessions, one parent noted how ‘there are not any [educational] toys in Maltese our little ones can play and interact with.’ Others agreed with this observation. Parents also raised concerns about children’s attraction to tablets and smartphones, noting how they interfered with social interaction. On the tail end of this discussion, one parent quickly added that ‘the toy must have something to make it feel like a toy and not a gadget.’

With further questioning, we also came to realise that different parents have different criteria when deciding to buy a toy. One parent told us that before buying a toy for her daughter, she would ‘try to see for how long she will play with it and what the toy will give her in return.’ Another parent, concerned about toys’ safety, checks for the CE mark (Conformité Européene) prior to purchasing the toy, saying that he associates the mark with better quality. However, he also confessed that ‘in the hands of children, nothing remains of quality. Give them something which is unbreakable and they will manage to break it in one way or another.’

Since our toy is intended for use in speech therapy, we went ahead and organised more focus groups with SLPs. Outlining the role of toys in their clinics, SLPs said ‘[they] are normally used as a reward. If you know that this child likes blocks, then you use them to motivate the child.’ Toys are also used as part of the language tasks SLPs give. ‘We use objects to put a grammatical structure in a sentence. Many times you find something that represents a noun, a verb, an object and then put them together’ to model the appropriate sentence construction. This prolific use of toys, however, brings with it a very practical problem. One SLP explained how challenging things can get on a day-to-day basis due to the lack of multipurpose toys. ‘We are always carrying toys… we are always carrying things around with us. Even our cars… it is like I have ten kids,’ she said.  

To address this issue, SLPs emphasised how useful it would be to have a flexible toy with multiple functions. One that does not bore children and which they can use to target different speech and language therapy goals. They also drew our attention to a prevalent but damaging mentality that they are trying to address. ‘Unfortunately, the majority of Maltese parents have a mentality that the more money they spend and the more therapy sessions for their children, the sooner the problem is alleviated, but in reality this is not true. The work needs to continue at home on a daily basis. It is not solely our responsibility,’ the SLP said. Much like when we practice daily to learn to play an instrument, speech and language therapy works the same way.

Sharon Borg, an experienced occupational therapist from the government’s Access to Communication and Technology Unit, said that the toy we had in mind could provide a simple way for parents to engage with their children and work at home on related exercises. Borg’s colleague, Ms May Agius, also noted the need for the toy to offer ‘surprises’, saying that ‘anticipation and elements of surprise draw kids and keep them engaged.’

Here we have only touched the surface of all the ideas brought forth. However, by considering the children’s, therapists’, and parents’ needs early in the engineering design process, we should be able to reduce the number of design iterations we have in future.

Reaching out

Design is key. Based on the feedback from the focus groups, we have now started working on the hardware and the software. But the journey is not straightforward. One issue we needed to deal with was the lack of compatibility between the 3D modelling software Flying Squirrel Games used and the technology used by the UM. From an academic point of view, because of the innovative nature of the toy we are making, we needed flexibility, so we modified Flying Squirrel’s virtual model to add different mechanisms which involve moving parts. These alterations now allow us to create support to fix electronic components within the device and ensure that no moving part is impeded by another part. As a result, assembly is much easier. 

Emanual Balzan and Dr Ing. Philip Farrugia

We have also made the decision to build SPEECHIE software using modular blocks. This will enable us to switch parts and functions around so we can widen the idea of who might enjoy our product. The toy will not only be of use to children with speech and language impairments, but also to others. This approach was inspired by a meeting with behavioural economist Dr Marie Briguglio who warned us that labelling the toy could be stigmatising. She explained that it should not become ‘an isolated toy which kind of becomes a label: because I have this toy, that means I have speech impairment.’  

Despite the aversion some parents felt towards technological devices, as said during focus groups, Borg also encouraged us not to shy away from using them. She said children with autism responded very well to technology, and therapists will make the best choice for the child to improve their skills. To hit a sweet spot in between these views, we are incorporating functions that will allow for a kinesthetic learning experience that involves physical activities rather than passive consumption of instructions. We want to mix different modes of play to encourage effective learning. We do not want kids to sit and watch their toy, but to move around, dance, and sing with other children. 

With all of these choices under our belt, we now have a working prototype. But the SPEECHIE toy is not yet complete. In fact, the coming months will see us working on the mechanisms and the interfacing of electronics. 

Towards the end of the year, we will start putting the toy into preschoolers’ hands to determine its effectiveness and efficiency in regard to speech and language therapy. To do this, we will compare the progress of children who use SPEECHIE with those who only use traditional SLP methods.

What we hope is that this toy will encourage parent-and-child interaction through play. We want to enable more frequent use of both Maltese and English and allow children to be safely exposed to technology and to a fantastic learning experience—all while having a ball.  

Note: We are excited to share these insights about SPEECHIE with the public, and if you would be interested in joining on this journey by participating in the evaluations, get in touch here: speechie-web@um.edu.mt

This research is financed by the Malta Council for Science and Technology (MCST) through the FUSION Technology Development Programme 2016 (R&I-2015-042-T).

Author: Emanuel Balzan

Living between two worlds

 

Cesar A. Cruz famously said that ‘art should comfort the disturbed and disturb the comfortable.’ People have placed plenty of emphasis on the second half of that sentence—art is often used to provoke and make the viewer rethink their perception of the world. But what about the first half of that famous maxim? Can art serve as a comfort to those enduring difficult times? Pamela Baldacchino, the artist who founded the Deep Shelter project, certainly believes so.

Baldacchino has experience with serious illness. Not only is she a qualified nurse, but she also suffered from fibromyalgia for 14 years, a chronic condition characterised by constant pain, fatigue, and trouble sleeping.

While reading for her Master’s degree in Fine Arts, Baldacchino created an audiovisual work purposely designed for a hospital environment. The work expressed empathy with patients by erasing the distinction between the sufferer and the audience, visually and symbolically showing states that merge into one another; the flesh of the artist’s hand becomes one with the ‘flesh of the sea’, for example. In another piece, the boundaries between sky, earth, and tree blur. She wanted to explore the concept further, to take her ideas beyond her degree and see them implemented in a practical manner within a clinical environment. With this goal in mind, she successfully acquired funding from the TAKEOFF Business Incubation Centre (University of Malta) as well as Arts Council Malta. Deep Shelter also forms part of the Valletta 2018 Cultural Programme and was presented during the Living Cities, Liveable Spaces conference held in November.

Others embraced Baldacchino’s approach to use art in helping those suffering from illness. A mutual friend introduced her to Dr Benna Chase, a psychologist within the Oncology Department (Mater Dei Hospital), who started using Baldacchino’s work during therapy with her patients. They then met clinical aromatherapist Marika Fleri, and the trio was complete. ‘We realised how much in sync we were. Through completely different mediums, we came together with instant understanding,’ Chase says.

 

As the Deep Shelter project, they have organised two series of sensory workshops, consisting of six sessions each, as well as artist workshops for the creation and donation of artworks to clinical hospital spaces. Some of these workshops were aimed at people in palliative care, many of whom are aware that they are nearing the end of their lives. The workshops aimed to help them recognise, create, and make use of the ‘language’ that art provides when words are not enough.

“It is difficult for patients whose lives are punctuated by clinical sights, sounds, and smells to feel in tune with nature.”

‘In one of the workshops, author Leanne Ellul started reading from Tereża, a book she translated about  a girl during the Second World War. Several of the patients had lived that experience and it took them back to their own childhoods. Then, we asked composer and percussionist musician Luke Baldacchino to pick up on the feelings conveyed in the writing, compose a piece of music, and play. We realised that something was happening within them,’ Baldacchino says. The most marvelous transformation was in an elderly woman who usually sat perfectly still and was almost totally unresponsive to the outside world. ‘While we were using spoken language, we couldn’t manage to get through, but then a piece of music brought a rare smile to her face. Through this alternate sensory experience, we were allowing processing to happen; it’s a form of therapy as well.’

Nature has always been central to the context of the Deep Shelter project; it becomes ‘a metaphor of the self, where both fluidity and tension are captured.’ But it is

difficult for patients whose lives are punctuated by clinical sights, sounds, and smells to feel in tune with nature. With the help of her aromatherapy oils, Fleri brings in an element of nature and tactility to the patients. ‘The kind of experiences we are trying to create are aimed at making the patient feel contained and held,’ Baldacchino explains. ‘We want to provide something that supports their gritty journey towards acceptance. Even if it does not fit into what we traditionally think of as contemporary art, it fulfils the scope.’ She expresses her frustration with the art in spaces where people are undergoing medical treatment that is merely ‘decorative’ or ‘clever’, and does not provide any sustenance to the patient’s emotional well being. There has to be a story woven behind the artwork that leads one to feel understood when they are going through a time of change, upheaval, or trauma.’

Baldacchino, Chase, and Fleri have received both support and contempt about the project’s goal to derive value from art for the process of healing. However, the patients that the Deep Shelter project has treated are unequivocal about its benefits.

One patient says she believes the workshops serve to ‘release’ emotions, while supporting them throughout their different journeys. When she felt that she had nothing to lose, the artistic outlet Deep Shelter provided gave her a way to release the emotions of anger, fear, and regret she had been holding within for so long. ‘The health system needs to be more open to other therapies to be able to provide a truly holistic healing modality, incorporating mind and body and not seeing the person as ‘parts’.’

Humans are the only species on the planet with the ability to tell stories about their life through art and sensual expression. But during the cancer journey, it is harder to find yourself and your experiences reflected in a meaningful way. The Deep Shelter project seizes art’s potential as a means to process illness, pain, and trauma and puts that power into the hands of the people who need it most.   

 

Author: Valletta 2018 Foundation
Photos: Eliza Von Brockdorff, Anna Runefelt, Sara Pace, Pamela Baldacchino, Tim Lewis

Blood, Genes, and You

Over the course of nine months, an entire human body is sculpted from a few cells into a baby. The blueprint is the information written into our DNA. But what happens if there is a mistake in these blueprints? Decades worth of research carried out in Malta and abroad have aimed to understand how these errors lead to a disease common in Malta and prevalent worldwide.
Scott Wilcockson talks to Dr Joseph Borg (Faculty of Health Sciences, University of Malta) to find out more.

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