SciMy Interview: Professor Datuk Dr. A. Rahman A. Jamal

interviewed by Dr. Wong Kah Keng

Prof. Datuk Dr. A. Rahman (MD, MRCP, PhD) is the founding director of the UKM Medical Molecular Biology Institute (UMBI) at the Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur. He graduated from UKM in Medicine in 1985 and obtained his MRCP (Paediatrics) from the Royal College of Physicians Ireland in 1991. He joined the Faculty of Medicine UKM in November 1991 and went on to pursue his doctorate studies in 1992 and was awarded a PhD in Haematology and Molecular Biology in 1996 from University of London, United Kingdom. He has since been actively contributing to Malaysian academic and research arena, specialising in molecular biology of cancers and thalassaemia.

Prof. Rahman is a senior consultant and professor of paediatric haematology and oncology and molecular biology. He has held numerous national and international appointments including the project leader for The Malaysian Cohort, Chairman for the National Stem Cell Committee for Ethics in Research and Therapy, Chief Scientist for the Space Science Programme for the National Angkasawan Programme (2006-2007), member of the Asia Cohort Consortium and also an editor for the Journal of Paediatrics and Obstetrics and Gynaecology. In this interview, Prof. Rahman shares with us his insights on cancer research and the space science programme, as well as the challenges faced to setting up an international class research institute.

Q1. What influenced you to specialise in paediatric oncology and subsequently PhD studies in molecular biology?

When I was a medical officer, I had my first exposure to children diagnosed with cancer. I immediately saw that this was a very challenging disease to treat. I decided to take up paediatrics as my specialisation and the field of haematology and oncology became my choice of subspecialty. With the desire to understand and be trained in cancer research, I decided to pursue a doctorate degree in 1992. I knew that the best environment to be a clinician scientist would be in the academia hence I applied to join UKM and was offered a scholarship to do my PhD. I was lucky as my PhD project involved looking at gene arrangements and mutations of the RB1 and CDKN2A genes in acute myeloid leukaemia. The PhD exposed me to various molecular biology and cell biology techniques.

Q2. You were the Chief Scientist for the Space Science Programme for the National Angkasawan Programme (MOSTI) in 2006-2007. Could you share with us your experiences of the programme?

I must first thank Datuk Dr. Mazlan Othman, the then Director General of National Space Agency (ANGKASA) who invited me to join the Space Science programme back in 2006. I was deeply involved in the contract negotiations with Russian authorities for the science experiments which we planned to send to the International Space Station (ISS) with our astronaut. The contract for the science experiments was an important component of the overall contract for the training of our two candidate astronauts. The procedures that our scientific team had to go to get approval from the Russian authorities were highly technical and challenging. There were 10 sets of documents which had to be submitted and approved. As we all know one of the main aims for sending our astronaut to space was for him to conduct scientific experiments in the ISS.

The biobank is part of The Malaysian Cohort (TMC) project – it is a national resource that we are building gradually and it is unprecedented by Malaysian standards

As this was the first time Malaysia had an astronaut in the ISS, he became an overnight celebrity and unfortunately the space science component had lesser coverage. Nevertheless all the scientists involved performed well and all the 5 experiments led by researchers from UKM (Cancer Cells in Space and Microbes in Space), UPM (Protein Crystalisation in Space) and UiTM (Endothelial Cells and Osteoblasts in Space) were successful and the results have been published in various journals. The coverage on the space science by the media was vastly overshadowed by the focus on our astronaut, despite the fact that the requirements, such as the bioethics, safety and security, hardware integration, experimental design, limitation of weight and volume, availability of equipments on the ISS, etc. that needed to be fulfilled for our space science experiments to be approved, were extremely demanding. To quote a prominent US space scientist’s words loosely, if one manages to pass the hurdles of getting a space experiment approved to be sent to the ISS, that alone is already a measure of success!

Q3.What were the space science experiments conducted?

I actually was given a chance of a trial run by Datuk Dr. Mazlan to send the famous nematode i.e., Caenorhabditis elegans, to the ISS in collaboration with researchers from the University of Colorado, USA in December 2006. This was successful and the worms (propagated in a liquid medium) was in the ISS for a total of 7 months. The results have been reported and published1-2. That gave us a good exposure on many of the processes involved in sending a space experiment to the ISS although the Russian way of doing things were a bit different in certain ways. For the October 2007 flight, our astronaut brought with him 5 sets of experiments. The key objective was to study the effects of microgravity on organisms and cells focusing on adaptation and also gene expression changes amongst others. I was the leader for experiment on Eukaryotic Cells in Space for which we sent Jurkat and HepG2 cells. Another experiment which UMBI led was the Microbes in Space where two types of bacteria were sent. Prof. Dr. Raja Noor Zaliha of the Universiti Putra Malaysia (UPM) led the Protein Crystalisation in Space which turned out to be highly successful. The lipases which she crystalised in the ISS had much better resolution compared to the ground controls. The UiTM group sent two cell lines (endothelial cells and osteoblasts) and have also published the results.

Space experiments are highly challenging – the scientists need to ask the right questions in terms of testing the effects of microgravity and radiation, have the appropriate experimental design, the containment requirements, the non-ideal conditions as compared to ground experiments, and the limited astronaut time and resources available to conduct the experiments. A space experiment usually takes around three years to plan and tested on the ground before sending it to space; we planned this in 18 months, and I believe the Malaysian scientists have done an excellent job which ensured the success of the space science programme, particularly in obtaining the scientific results.

Q4. UMBI is home to the largest biobank in the country3. How does the biobank contribute to local research scenes?

The biobank is part of The Malaysian Cohort (TMC) project4  – it is a national resource that we are building gradually and it is unprecedented by Malaysian standards. We started recruitment in 2007 and in September 2012 we concluded our first recruitment phase at 106,527 participants, way past our target of 100,000 individuals. We collected data on demography, medical history, family history, environment exposure, as well as lifestyle factors including diet and physical activity. Comprehensive biophysical measurements were done and also blood tests. Blood and urine were collected and these were processed and stored in both -80o C freezers and liquid nitrogen tanks for future research. As we know, the first and famous cohort study was the Framingham Heart Study (FHS) initiated in 1948 that followed a group of people throughout their lives to identify risk factors to heart diseases. The FHS is still ongoing by following up the children of the original participants of the study. A cohort study is excellent in identifying risk factors and early biomarkers for diseases – it takes time for events, or diseases, to occur. A casecontrol study is not the best model although easier and less costly to do. A cohort study follows the individuals from the time when they are healthy or asymptomatic to development of diseases.

The Malaysian Cohort Biobank follows closely the protocol and standards from the UK Biobank that houses the data and bipspecimens from over 500,000 individuals. The UK Biobank has conducted a lot of validation procedures including stability testing of biospecimens or bioanalytes stability and systems management. The Malaysian Cohort is now in the follow-up phase and we are repeating the interview, the biophysical measurements and the blood tests and also storage of blood and urine. There is a huge potential for many research projects studying changes involving lifestyle, genome, proteome or metabolome alterations that occurred within that five-year period and link them to diseases. The Malaysian Cohort (the vast database and the Biobank) is a valuable national resource and the value will certainly increase with time.

This amount of funding pales in comparison with that of, for example, the Cancer Science Institute (CSI) of Singapore that was awarded SGD172 million grant by their government

Q5. What are the challenges faced by institutes with the Higher Institution Centre of Excellence (HICoE) status?

The biggest challenge is sustainability. I think the government has tried hard to improve local research arena but our central research funding remains insufficient. For instance, one cannot expect to produce a research institute with international prestige with a mere RM3 million of funding annually. This amount of funding pales in comparison with that of, for example, the Cancer Science Institute (CSI) of Singapore that was awarded SGD172 million grant by their government at inception in 2008. Hence, I think the central funding pool for HICoE institutes needs to be increased significantly and also to create more research positions – all of the successful overseas research institutes have a critical mass of principal investigators (PIs) supported by a team of postdoctoral researchers, an aspect that we are lacking due to insufficient funds to sustain postdoc positions.

Q6. Do you think that local researchers should participate in whole genome sequencing (WGS) studies on cancers?

I think this is the best time to do this when the cost of sequencing is much lower than it was before. Our funding committees must be aware of the trends in research and genomics medicine is now top of the list of priorities of many nations. The way our grant proposals are evaluated needs to be changed and we need to bring in the appropriate experts into the panel. If we do not have Malaysian experts in cancer or genome research, nearby regional ones should be recruited to identify truly novel and worthwhile cancer research projects. Cancers are very diverse even within the same subtype, and WGS is crucial in subgrouping the cancers for targeted therapies. The Cancer Genome Atlas (TCGA) project has finetuned different types of cancer classification but there is still a gap as many of the samples are not from this side of the world, a potential that we should definitely explore.

Q7. What are some of the strategies that Malaysian cancer researchers should adopt?

We should focus on cancers that matters in Malaysia and have unique phenotype specific to our populations e.g., for colorectal cancer, we seem to see it occurring relatively younger in Malays compared to the Chinese. Few nations, if at all, are motivated to answer such question except us. Also, we should encourage multi-centre collaborations e.g., among the local universities with the Ministry of Health as they treat the largest number of cancer patients nationwide, and hence possessing huge number of cancer samples. Besides, we shouldn’t work on too many different cancers – the government should address the key types of cancers relevant to us and with the capacity to perform well internationally, and to prioritise funding for these specific researches.

Q8. Finally, what are the advices you would give to young scientists?

I encourage young researchers to look for opportunities outside of Malaysia or to obtain a postdoctoral position overseas. The exposure and the skills acquired in a top laboratory outside Malaysia will be valuable. I am not implying that we do not have sufficient number of PIs to train local talents but when one is trained in developed countries, one would be exposed to the best in research with cutting-edge technology. They will also forever be linked with their supervisors or institutes, and able to bring back the networking to Malaysia for future collaborative projects. Finally, young scientists should not say ‘no’ too early in their career. By taking up various challenges, sooner rather than later opportunities start to knock on one’s door, and thus young researchers should take up the challenges presented to them even if it means one has to walk the extra mile and work the extra hour.

This article first appeared in the Scientific Malaysian Magazine Issue 10. Check out other articles in Issue 10 by downloading the PDF version for free here: Scientific Malaysian Magazine Issue 10 (PDF version)

References

[1] Jamal R et al. J Am Soc Gravit Space Res. 2010;23:85-86.
[2] Then et al. Asia-Pac J Mol Biol Biotech. 2014;16:47.
[3] http://www.ukm.my/umbi/biobank-sample-log-in/
[4] Jamal R et al. Int J Epidemiol. 2014; doi: 10.1093/ije/dyu089