Global Editions

SynBio takes centerstage

by Aasim Zafar Khan

Dr Faisal Khan is the founding director of the Institute of Integrative Biosciences at CECOS University, Peshawar. He completed his doctoral studies on the intersection of Cell Biology and Systems Biology at the University of Oxford, where he was a member of the Oxford Protein Informatics Group. Dr Khan works closely with the provincial government of Khyber-Pakhtunkhwa (KP). He is a member of the KP IT Board, the Advisory Committee at the Directorate of Science and Technology, the Higher Education Research Endowment Fund and the KP Youth Development Commission. He is also the brain behind Peshawar 2.0 that runs Basecamp, a coworking space, and Revolt ‘the startup factory’ in Peshawar. He is also the principal investigator of SynBioKP, a flagship synthetic biology project of the government of KP and the Precision Medicine Lab, which is part of the recently launched National Centre for Big Data and Cloud Computing. Under his mentorship, two teams from Pakistan participated in the iGEM competition in Boston in 2016 and 2017, bringing home bronze and silver medals, respectively. MIT Technology Review Pakistan sat down with him to discuss his research interests in microbiology and their application in Pakistan, as well as his work with the public sector.

Tell us about your research interests.
My doctoral thesis was about the application of Artificial Intelligence in cell division, and by extension cancer, which is uncontrolled cell division. It applied lessons from graph theory akin to social networks analysis to study proteins.

Read more: Of unexplored avenues: Microbiology and Pakistan

In a cell, a protein doesn’t work alone, it works with say, a hundred thousand other proteins, in the form of an army. I wanted to understand who they [different proteins] were talking to and what did the neighbourhood look like. The idea is we can understand unknown proteins through the known function of proteins in their vicinity, and the neighbourhood in general. We’re now using this knowledge to understand infections like dengue, hepatitis and malaria in my lab in Peshawar.

This method can also let us narrow down drug candidates. The idea is to use all the data and layer it on top of the network of proteins, then use AI to find candidates with highest probability and finally, take the findings to the lab to see if the machine’s predictions correspond to what’s happening in reality.

Using this technique, I was able to find 26 previously unknown proteins for their role in cell division in my thesis research.

What are some of the key concerns in biological research? How do you assess the state of the field at the global level? And how do you compare it to our local context?
From a very pragmatic and Pakistan-centric perspective, we ought to realize that laboratories for biological research are like kitchens. Everything is alive and there are a lot of perishables. This makes biological research an expensive endeavor, and is the reason why we don’t see many functional labs.

Researchers are no longer doing just microscopic analysis of cells.  Nowadays, we’re looking straight at the level of the molecule, adding another level of expense so even if labs have the required equipment, they need constant stream of funding to keep things in action. Thus, resource constraint can be a bottleneck.

The other bottleneck has to do with a surge in interdisciplinarity and increasing cross-talk among different skill sets. Biology is becoming data driven. For example, biology students generally are not very fond of mathematics and statistics, but now you can’t be a biologist without the knowledge of data science. How do you make students develop an interdisciplinary interest is a key question facing academics in Pakistan where students are forced to choose between mathematics, computer science and biology at a very early age.

Of late, machine learning and AI have also entered the field because huge datasets are now available for work. As a researcher, sometimes I don’t even need to come to a lab, if I have my laptop and an Internet connection. Look at it this way: every living organism or species has its own unique DNA content or genome. There are millions of species, so millions of genomic sequence data is out there. Most of these and many other kinds of sequence data is already available in the public domain free of cost. You just need to browse them, ask the right kind of questions and dig out your answers.

The broader question the scientific community in the field of biology faces today is: how do we connect the DNA code we’re able to read (and copy and paste in a text file) to a phenotype (clin-ical and physical manifestations of the DNA code). We know there are certain genes, stretches of DNAs that cause something (a disease, or some other function), but we don’t yet thoroughly understand the remaining 90% of the total genome for every species.

Things are developing really fast and costs are going exponentially down. We just need to compare the cost incurred on the first human genome project to what it costs now. It took more than a decade and required $3 billion, compared to now when it can be done for a thousand dollars. This takes the growth in DNA sequence data to a whole new level, ushering in new unprecedented opportunities.

There’s this fad with genome projects that can have multiple applications, including figuring out lineages. Is that kind of work possible in Pakistan?
We have moved past the time when studying an individual’s genomes was a big deal. People are now talking about hundreds of thousands of genomes being sequenced. In the United Kingdom, their Genomics England project has set out to sequence the DNA of a 100,000 individuals from different ethnicities and disease backgrounds to understand differential patterns of variations in the genome. There are similar projects in the United States and Qatar. Luckily, we have the high-tech equipment required for such an endeavor in Pakistan as well. The Aga Khan University in Karachi and Rahman Medical Institute in Peshawar have state-of-the-art Illumina machines. At the latter, we have just received a grant to launch a Precision Medicine Lab to undertake the country’s first ever National Cancer Genome Project. We plan to sequence DNA samples from 100 cancer patients initially to improve our understanding of different types of cancers and propose more targeted (hence precision) and effective treatment options.

We need to keep in mind that across diseases, the medicine prescribed to patients here haven’t been tested on people in our part of the world. Instead, they’re tested on samples representative predominantly of Caucasian origins in the US. So the side effects and other information mentioned for medicines may not be entirely true for our population. That’s where precision medicine comes into play because even for a single individual, two cancerous tumors may have different characteristics (intra-tumour heterogeneity), needing different interventions. We’re hoping that the cancer project will help us test drugs locally.

As the team supervisor and principal investigator, your role was crucial in securing positions for the Pakistani team at the iGEM competition at the Massachusetts Institute of Technology. Tell us the backstory of the project.
iGEM was born out of a course taught at MIT in 2004. Over time, it budded off as a competition which has since then gone viral with students in related fields of study from across the world. Around October each year, Boston is full of undergraduate and graduate students from across the globe who compete with their synthetic biology (SynBio) projects involving engineered living bacteria, yeasts or plants.

For us, the experience came with a lot of exposure for students participating in it because of the accelerated learning environment.

Initially, we had to convince the KP government to cast the net far and wide and let students from across the country participate. In 2016, we got students from Swat and Waziristan to Hyderabad and Kalat. The student from Kalat was particularly memorable. He took a 26 hours bus ride to reach Peshawar and go straight into his final interview for the iGEM Peshawar team, defying all the heat and stress of the journey. He just graduated as a gold medalist from Balochistan University. Another student left Karachi University and transferred his credits to CECOS and moved on to become a mentor of the 2017 team. A couple of participants are now running their own startups, others got scholarships abroad, so you see a community is building up around that one project.

The format of the project is such that participants from across the country stay with us in Peshawar for a three-month period. We pay for their boarding and lodging. During the stay, they attend several classes, hands-on trainings, brainstorming sessions and team meetings. Since its a student driven endeavor, they throw ideas on the table and we help them sift through. The most important features of a good iGEM idea is that it builds on existing DNA resources (called bio-bricks), it is manageable in the time and resource constraints and for us, the most important characteristic is that it addresses a pressing problem relevant to the Pakistani context. The result is a team of 12 to 14 people whose sole focus is to solve that particular problem.

There is also an outreach component in the project. The two iGEM Peshawar teams we mentored here have reached out to more than 20,000 high school students who are now familiar with Synbio and its concepts.

At this stage, we’re thinking about scaling the project but all of this has been made possible because we put together a team, delivered our objectives and demonstrated to the government that there’s potential for cutting-edge synthetic biology research. It took a lot of effort in the beginning to convince the government but we were able to seal the deal when the first iGEM team won a bronze medal in Boston. It showed them that the funding was not only useful and pivotal for our economy but also practical and possible in Peshawar using local talent.

The next phase involves working on industrial applications since most of our industry is based on biological products, i.e. food, feed, fabric, leather, etc. We have the whole turf in front of us and we need to begin work swiftly to stay in the race.

What kind of interventions can SynBio make in Pakistan?
Synthetic biology is a new area. It involves designing genetic circuits on computers, and then getting them printed chemically using over the cloud services. You can put the printed DNA circuit into your bacteria and yeast and make different products of choice. For example, you can make rose oil, without needing roses, spider silk without the need for rearing spiders and valuable drugs that are only found in rare herbs, without needing the herbs anymore.

You can also go slightly more intelligent and build biosensors that take an input and give out an output on the basis of some problem they solve. One of our winning projects in 2016 used bacteria to detect carbon monoxide, which is a poisonous but odourless and colorless gas that kills many people in winter when people use gas heaters. The project used bacteria to give out red color ‘alerts’ if it detected the gas in the atmosphere. All of these synthetic biology feats have been made possible due to the decreasing cost of DNA sequencing and DNA synthesis

The ingredients of food and leather sectors run into hundreds of millions of dollars. We have a chronic problem of trade deficit. If we seriously set ourselves some milestones, we may stop importing and, who knows, we may start exporting in a few years if we invest seriously in synthetic biology.

There are dozens of students already trained in SynBio, besides, there are thousands of unemployed biotechnology graduates who can be tapped into for this kind of work. If we can put all these resources together, we can easily achieve our milestones and meet our needs. That’s how people have done it elsewhere. In Singapore, a $2 billion industry was set up with lesser number of biology graduates. They were able to curate the sector well by setting a coherent strategy with milestones and offering funding, infrastructure and training  to researchers.

And the good thing is you don’t need high end labs with PhDs for this kind of work anymore. Do It Yourself (DIY) labs have emerged across the world. With decreasing costs, you can do biological research in your house garage now. In fact, garage biology is already a phenomenon, demonstrating how cutting edge biology has democratized and how innovation is going to accelerate as a result at all levels. If we keep ignoring these developments around synthetic biology, Pakistan will miss this wave, just like the IT wave did in the past.

We need to reckon with the fact that a lot of biology education happening in the country is simply outdated. Take the example of the Golden Rice Project, under which the staple was fortified with vitamin A at a cost of around $100 million using traditional biotechnology and genetic engineering methods. Now, the same kind of work can be done in $5,000-10,000 using synthetic biology. So there is no point doing, or teaching, the former in Pakistan when we can do the latter. It makes absolutely no economic sense to continue teaching biology using traditional methods. We need to leapfrog – like countries did from 2G to 4G in the telecom sector.

Read more: Pakistani Professor Wins UNESCO Prize for Microbiology

You’ve worked with policy-making bodies as well. What have you been able to do to strengthen policy-research linkages.
My association with these bodies started accidentally. I was reluctant in the beginning but was still dragged into several policy-making bodies and committees. In retrospect, I think that gave me a lot of exposure. One thing I found out was that there is huge mistrust between the government and academics. The former, like any funding body, seeks tangible outcomes, and believes that the latter haven’t delivered much.

As a young PhD, I pitched and said to them can we stop doing what we have been doing, and instead focus on waves we can catch. Since my area was biology, I suggested we give SynBio a shot. That’s how SynBioKP was born and the iGEM project got funded. And the fact that we delivered and secured awards in the US really sealed the deal for us.

At the Higher Education Endowment, I was the youngest on the board. I had to put my foot down and convince them to try and experiment with the grant making procedures. I helped redesign the application process, got them to make sub-committees to go out and study procedures of other funding bodies and revamp the procedures. I’m hoping there will be some trickle down effect.

At the KP IT Board, I pitched early age programming, a digital district, co-working spaces and have spoken on behalf of the private sector. There’s a growing startup scene here that needs to be sustained. Thankfully, the government is listening.

What does the local landscape of research in biological sciences look like? How far does Pakistan lag behind on genetic research?
It is in bad shape. I have hardly come across a lab that is properly funded. People are just doing whatever research they can within existing resources, but that research doesn’t have many applications. The most common kind of work you come across is concerned with growing bacteria, and testing their anti-microbial and anti-everything activities. This is very rudimentary, and I’d say that about 60 percent of student theses are about such anti-microbial activities.

What we really need is some thought leadership. It isn’t just about money, but also about setting an agenda and identifying strategic thrust areas that can guide scientists to take up research in key areas. We can’t leave it entirely to them (researchers) because then everyone might pursue their little problems that may or may not fit into the larger national agenda. We need consistent and substantial funding over a period of time and we really can’t afford to spray money on irrelevant problems which unfortunately most of the funding bodies are doing.

I’d say the situation is depressing as well as optimistic. At the moment, people at the helm aren’t well updated, but time is on our side. Very soon, we’ll have many more tech-savvy people in positions of authority. In a nutshell, I’m optimistic about the future, but there are hurdles, financial as well as capacity related that prevent innovation at scale and keeping us from reaching the inflection point. Technology does not wait for anyone and we really need to solve these issues and solve them urgently.

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