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Exclusive Interviews with Innovators Under 35

Have you ever thought of what impact you could have on our society? Some people are different; they have innovative minds and invest their time developing ideas in the hope of bringing those brilliant thoughts to full blossom. Each year, MIT Technology Review (TR) magazine elects ten young innovators who are below 35 years of age on a regional list to award them for their innovative work that potentially makes huge differences in society and lives. All 10 Asian honourees in the year of 2016 delivered pitches on their innovation during the two-day EmTech Asia conference and APBN is honoured to feature the following innovators who are truly inspiring in their respective fields.

I. Dr Angela Wu, on genome editing technology

One of the winners of Young TR Innovators Under 35 in Asia award, Dr Angela Wu Ruohao, is the founding member and scientific advisor to the Agenovir Corporation, Australia. She is now the Assistant Professor of Hong Kong University of Science and Technology. Dr Angela is instrumental in launching Agenovir, which uses genome editing technologies to cure chronic viral infections. Using genome editing technologies to target destruction of viral DNA instead of human DNA, Agenovir’s future products will be able to remove these viruses from the cell, resulting in a permanent cure.

How do you feel about making MIT Technology Review magazine’s annual list of the young innovators under 35 in Asia?

I am very excited and honoured because all the other candidates are also doing exciting and great things; at the same time, I also feel humbled to be among these amazing peers.

What are the aims for your current projects or research?

I am an assistant professor in the Division of Life Science at Hong Kong University of Science and Technology. My research focus is on inventing new technology and tools with high resolution imaging for the study of individual cells in our body. Take the liver for example: we often think of that as a whole, but we don’t often consider that a liver is actually made up of millions of individual cells that have diverse functions. If a cell mutated, what kind of impact does it have on the rest of the organ? What is the role and function of this particular cell in the liver? Previously we looked at certain aspects of that cell, for example RNA. In my lab, we are trying to figure out new technology to look at more than one facet of the cell, maybe look at both RNA and DNA, or DNA and protein, at the same time. Accessing more aspects of the cell allows more information of that cell to be used for medical purposes. We are also investigating disease mechanisms using novel approaches such as single cell transcriptomics and gene editing. My ultimate research goal is to help bridge gaps between biology and engineering.

You co-founded Agenovir which is using CRISPR-based gene editing technology to solve healthcare problems. Could you tell us what part you have played in launching Agenovir?

In our start-up company, Agenovir, I got to wear a lot of hats, be it the grant writer, public relations, human resources (deal with hiring) or helping in the lab and planning experiments. I think a lot of skills are required to run a company and work with investors. As the “investor pitcher” and “scientific planner”, I contributed by helping my company to get Series A funding successfully. But now that I have my own research lab in HKUST, I put most of my effort on my own research group, and have transitioned to being an advisor for the company.

Could you briefly explain the use of genome editing technologies in the treatment of chronic viral infections and the success rate of such treatment?

The general idea of CRISPR/cas9 is that an enzyme that can make cuts in the DNA will work together with a guide molecule that acts as GPS, and this GPS molecule will tell the cutter enzyme to go to where we want it to go and cut in the genome. There are a lot of viruses which cause disease by inserting their viral genomes into the human genomes when they infect human beings, and this inserted viral genome will stay within the host body for the rest of the person’s life. As our goal is to remove viruses from human genome, we can tell the GPS molecule to target the viral sequence that had been inserted into human genomes, then the enzyme will go cut it out and we can even put back the correct sequences that were supposed to be before any mutations took place.

In the process of cutting out the viral genome from human genome, will this action affect the immune system of the body?

Not really. When you get infected by a virus, your body starts to make viral proteins and your immune system recognizes those viral proteins, and input that data into the ‘database’ of the immune system. Hence, even when we cut out the genome of the virus from our DNA, our immune system will still have captured a record of what that viral protein looks like. So CRISPR won’t be destroying the immunity that you have already built. Another thing is that viruses are always evolving, and so the genius of the CRISPR system is that we can always change the guide molecule. We can design new guide molecules and target the evolved virus and repeat the process.

Are there any challenges being in the management role in a start-up company?

In my role at Agenovir I did not face many management challenges, mainly because we had such a fantastic team. At the beginning, the company was really small and there were just a few of us, and we always had good communication between team members. We have our all-hands meetings every week to discuss the direction of the company. During those meetings, everybody can get informed and on-board with the company decisions and directions. Some people will suggest decisions based on scientific consideration, and for someone with more managerial experience might come in with perspectives on market, or timelines, and recommend different things to prioritize. We typically discuss until everybody is on board and on the same course.

As an innovator yourself, what do you think are the essential qualities that innovators/entrepreneurs should have?

I think entrepreneurs and innovators come in a lot of different sizes, shapes, and flavours. My co-founder at Agenovir is an academic scientist, but I think his curiosity and strong interest in what he is doing is really what drives the science in the company. My personality is quite different from his, and in addition to science I really enjoy the interpersonal aspect of the process, and I’m also very good at juggling many different tasks. But both of us made important contributions to the company, and we communicated and worked really well together. If you want to start a company, you might like to look for partners that complement your own skill sets to make a good team.

Where do you think genome editing technology is heading to?

I see it as a promising field which will probably generate a lot of surprises for us in the future. There are several clinical trials, starting this year and I think it is very promising but at the same time, entrepreneurs and scientists, as well as policymakers should consider any potential risks and ethical aspects in anticipation of these scientific breakthroughs. At Agenovir we also very actively considered these aspects in our development plan.

II. Dr Dhesi Raja, on applying artificial intelligence in medicine and epidemiology

Dr Dhesi Raja is another awardee of the TR Young Innovators Under 35 for his work in artificial intelligence in medicine. Dr Dhesi Raja is a medical doctor and completed his master and PhD degree in epidemiology in Malaysia. He co-founded the Artificial Intelligence in Medical Epidemiology (AIME, pronounced as ‘Amy’). Combined with machine learning techniques and epidemiology, weather and geographical data, the AIME platform is capable to predict outbreaks of diseases such as dengue and Zika up to three months in advance.

Dr Dhesi Raja had previously worked in the Minister of Health in Malaysia and carried out some short programmes with WHO and UN.

Could you tell us more about the AIME platform which you cofounded?

When I tried to identify the problem in public health, I realised that statistics is main tool to predict the epidemiology but they are limited to time and space. But a problem is by the time you complete the data collection, validation and analysis, the data or information become outdated. With that, it is not possible to contain the abrupt disease outbreak.

It all started from a competition, Global Impact Competition that I joined in Kuala Lumpur, Malaysia. I won and got chance to go to Singularity University in Silicon Valley. There, I presented my idea about artificial intelligence (AI) and my team got the FIX (Free Innovation Exchange) grant to go to Brazil. We used 270 variables such as rainfall, wind speed, wind direction, thunderstorm, a lot of variations, type of houses, satellite images, and others, for the prediction of disease outbreak in Brazil. Brazil government was happy and wanted us to help them for the Rio Olympic Games. We have not published the work for Rio, but it was really good and achieved accuracy of 84.6%.

We won another competition in King’s College, London and was the top 8 in Harvard University. Then we got invited to help the Philippines with disease prediction in the city of Manila. Currently, we are in the midst of talking to the United States, and we got a funding from a telecommunication company named Webe Community, which is supported by Telecom Malaysia.

What is the degree of accuracy of this predictive platform?

In two states in Malaysia, we achieved 88.7%; in Brazil, we achieved 84.6%; in Philippines, we achieved 84.11%. The accuracy differs due to the geographical aspects of the area. I wouldn’t say the areas covered in Malaysia are highly populated but in Rio de Janeiro, Brazil, it is highly-populated and there are a lot of favelas. Thus the accuracy is about 4% lower there.

Could you tell us about the newly launched mobile app platform?

All the previous projects are web-based and are funded by the governments of different countries. We provide the sense of security for decision makers who are public health physicians, epidemiologists and ministers with predictions which are three months in advance.

Then it came to me: why not we create a mobile platform? We then decided to create a mobile application in Malaysia. I told Malaysia government agency that Dengue and Zika is a community-based disease. Only with data sharing and work together with the community, the country can do more for the disease prediction and cleaning the potential breeding site for mosquitoes. Thus, for our technology, we have some data from public and cross validate with the data from government agencies and because is validated data. We released the app on Feb. 24 and can be found on all the Apps store and Android store.

Everyone can create and put an app in app store but how many people will actually download and use it? Even being scientists, we have to think like a businessman sometimes to create stickiness in our mobile app. I spoke to the Telecom company, instead of people running around chasing the Pokemon, why don’t we run around and chase the breeding sites, snapping the photo and uploading to the system. After checking, the city council will clean the area if it is approved. The end user will then get free credit and data plan. It is a win-win situation where the user gets incentive and the council gets the information to clean up the breeding site. Currently the mobile platform is launching in Malaysia only because it is sponsored by Webe Community and Telecom Malaysia;the other countries are web-based AIME platforms.

Would you think that putting efforts in eradicating mosquitoes, the carriers of Zika and dengue viruses, is more significant than predicting the spread of the diseases?

It is important to understand the infectivity rate of a mosquito. Do you know that the chance of a mosquito carrying dengue virus is less than 2-3%? From an epidemiologist’s perspective, I think it is not necessary to remove mosquitoes completely from ecosystem. Rather than eradicating the mosquitoes, humans sometimes breed the species in some less noticeable areas.

We do not know exactly how is it contributing to the ecosystem yet, but we feel that it is a bad choice to simply eradicate something from the planet unless it is directly affecting mankind like small pox, which killed billions of people and we knew a particular virus is the cause of the disease so we eradicated that virus. Thus, I think the focus should be predicting to mitigate before the outbreak happen, rather than removing the mosquito from the ecosystem.

What is your future vision?

I am envisioned AIME to be the next Google platform for people to obtain information on the potential outbreak of infectious disease. I hope in the future people will rely on AIME to check whether it is safe to travel to certain countries or continents within particular periods before booking their flight ticket.

How do you feel being awarded as one of the young innovators under 35 on MIT TR magazine’s list?

My first award was the King’s College award and followed by the Harvard award, and then I have been awarded as one of the top ten scientists from United Nations, and this is my fourth award. I believe every award is a learning curve for me and they validate my enthusiasm and my research. We should be humble and continue to learn from our co-founders and also other scientists.

Are you also working on an online health portal?

Yes, I am one of the founders of Malaysian Medical Gazette, an online bulletin reporting on health news and information. It is difficult for the community to understand the scientific journals. Currently we have 26 doctors, editors and translators to translate journals and also write articles in Malay and English. We publish articles three times every week and today our website has about ten thousand visitors daily. The purpose of our website is to empower the community and spread public health knowledge. We all work for a good cause.
(Check out the website at www.mmgazette.com)

As an excellent innovator and entrepreneur yourself, what do you think are the essential qualities in innovators/entrepreneurs?

Some people might say ‘you got to work hard, persistent, or dream the impossible’. For the young innovators, I would say ‘Never believe or follow the experts because experts are the one who will tell you why you cannot achieve things in that particular field. Their statement might not be accurate. Thomas J. Watson, the founder & CEO of IBM, where he said that this whole world only need 5 computers but today every one of us have our own computer. When innovating, always fall back to the theory of reasoning, and always reason yourself when you try to achieve something.

III. Dr John Ho, on creating micro-sized bioelectronics for patients

At the age of 28, Dr John Ho is already an Assistant Professor in the Department of Electrical and Computer Engineering at National University of Singapore, and he is also listed on the Forbes 30 Under 30 Asia in the Healthcare & Science category. Dr Ho won the TR Innovators under 35 award for his pioneering research on the development of wireless technologies for bioelectronic systems that can be used to help treat intractable diseases, such as cancer and diabetes. He has been developing new wireless technologies that could help to reduce the size of current, bulky bio-electronics such as pacemakers. By enabling smaller bioelectronic devices which are capable of working deep in human bodies, such technologies could one day enable doctors to prescribe a tiny, wireless device instead of a pill.

How do you feel winning the award as a young innovator under 35 and making the MIT TR magazine’s list? How would you describe the importance of your innovations?

It feels great to have your research get recognized. It is quite humbling, as many amazing people have won the award. Previous global Innovators Under 35 lists include renowned personalities such as Google’s founders Larry Page and Sergery Brin, and Facebook’s founder Mark Zuckerberg.

My research focus is on wireless powering for bioelectronic devices. The importance of our study is to enable very small devices to put into human body in the future and of which can be operated for very long time. That is something that is not possible today. Today, the devices are quite large in size and the battery will run out and causing them to stop working.

What made you started what you are doing now?

I was an electronic engineer. I was born in California and grew up in the Silicon Valley. I studied electronic engineering. After working in a software company, I decided to do graduate school. I enjoyed research and discover new and exciting things. I got into research and develop products and in the lab, I was doing crazy thing. One of the things I love about research is that there are people from all different backgrounds coming together to tackle problems. You have to find out and learn the skill sets through dealing with the problems, rather than matching the problems to your skill sets.

What are you focused at, and what are the others that you are currently working on?

Much of my current work is on developing wireless technologies to transfer power and data to tiny devices implanted in the body. We demonstrate many of our technologies in cardiac applications. The first implant in the world was pacemaker. Our wireless technology enables devices to be wirelessly powered, which means that they do not need large batteries to last many years in the body, and that’s why they can be so small.

We are also fascinated by the idea of utilizing light. We work on the implant that can emit light at certain wavelengths in order to control certain biological processes. We have also been working continuously to develop our wireless technology, and investigate how to continually engineer the electromagnetic properties of the object that is put in your body, and how to use that to shape the field inside your body.

Why is it important to reduce the size of bioelectronics? How can it be done?

The importance is: accessibility. The smaller the device, the less invasive it becomes to implant the device, which makes them more available for interventions. Currently, most devices like pacemakers are placed in the chest cavity and there are tons of wires and often cause a lot of problems. In future, as electronic devices become more sophisticated, we can certainly think about accessing many more organs inside the body: your brain, pancreas, liver, and even cancer or tumours grown inside your body. If all these places become accessible, new medicine can be invented to fix them.

Can you outline some considerations necessary for the achievement of small-scale bioelectronic devices?

Power is always the biggest consideration. Today, electronics are very miniaturized, I can make devices that incredibly sophisticated. I can make very complex microchips that are just a few mm in size. But the problem is how do I power it - these devices need power in order to function normally. Power is the biggest consideration and that is why I chose to work on wireless powering. Other considerations are processing and biocompatibility such as how to do the interface.

Will the devices interfere with other gadgets surrounding?

The power around your body is quite low and also your body is not very transparent to radio-frequency electromagnetic fields. So typically, the implant device will not interfere with other gadgets in the environment.

As an innovator yourself, what do you think are the essential qualities that innovators/entrepreneurs should have?

Persistence. Genius is overrated. You don’t have to be a genius to be a researcher. Day to day, research can seem quite incremental, and things often don’t work. I have been working on wireless powering for almost seven years, from my PhD years until now. What makes progress possible is persistence, the ability to work day in and day out on goals that you believe are truly important.

Click here for the complete issue.

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Healthcare Focus: LUNGS
Get to Know TCM
Diabetes: The Big Picture
The Piece of Your Mind - Brain Health/Science
Advocacies in Support of Rare Disease Patients
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Eye – the Window to your Soul
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A change of heart — Cardiovascular diseases
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