This will be, I think, a shorter talk, and it's really more light than heavy in the sense that we're just simply trying to look at where, or I guess more an opinion piece of where I think metabolomics is going. The idea is to sort of inspire you to sort of, I guess, suggest some things where you might want to explore, but also to encourage you to explore. So over the last 10 years, metabolomics has grown quite considerably, and this is just simply doing a PubMed search, looking at terms for metabolomics, metabolomics, metabolome, and metabolome. You could do a PubMed search right now, and you'll get very similar numbers, but it's actually growing exponentially, which is quite something. The question is, where is it going to go after this? Is it going to continue growing? Is it going to flatten out, or is it going to plummet? And how it will proceed over the coming years is actually defined by where there are some critical bottlenecks in metabolomics that would either prevent it or allow it to realize what its real potential is. So I think you guys have already seen the first bottleneck, which is, in the case of trying to do untargeted LCMS, it was a lot of work. It's not particularly automated. I think you can also see that there are real challenges with the level of coverage that we get. I've brought up some of those points in earlier lectures, but you can also see from whether it was the untargeted data or the NMR data or the GCMS data that you're typically working with 50 to a couple hundred compounds that are identifiable. Metabolomics is really expensive to get into. I've mentioned a little bit, to some of you, I guess the Metabolomics Innovation Center, which is a center that I've been running for the last five or six years. NAMA is part of it, and Jeff was involved with it in the early days. It's based in Edmonton. It's distributed into different cities in Victoria and McMaster University in Hamilton and McGill University in Montreal. And all together, there's $30 million of equipment that is in this center. So it's not something that someone can just say, I'm going to do this tonight. It's a lot of work to build out. It's a lot of work to maintain. And so if that's the barrier to get into metabolomics, then it's too big a barrier for most people. There's a central issue in metabolomics, which is about quantification. I've been emphasizing that. And you guys saw this as well, where we had quantified data for the targeted work, but for the untargeted work, all of the data is non-quantified. It's only relative. Another central issue with metabolomics is that people are finding cool things all the time, but are we actually seeing metabolomics being used in the clinic? Are doctors showing up on TV advertising their metabolomic applications? And then I think the other key issue, especially with small molecules, is drug companies are the elephant in the room. They are the ones with huge R&D budgets. They're the ones that often direct and decide where major initiatives should be. They're the ones that really said we should do genomics. They're the ones that said we should do proteomics. So if you can make metabolomics matter to drug companies, that also will help sort of clear some bottlenecks. So those are bottlenecks. So there are some trends that are happening to essentially address those. One area people are working on is automating metabolomics. Another area people are working on are trying to expand the metabolome coverage. Another area is trying to make metabolomics more portable. Another area is obviously moving more towards quantification. Another area of active work is metabolomics moving from the lab to the clinic. Another one is trying to get metabolomics back into drug development and discovery. So I'm going to talk about each of these points over the next 40 minutes or so. And the first one I'll just talk about is move toward automation. So this has already been hinted at. So there are now more and more types of equipment that are automating metabolomics. So I mentioned the juice screener and wine screener. This is something that Broker developed a number of years ago. Well, four or five years ago they've also got one that does lipid analysis that came out last year. So these are NMR instruments. Can't even tell that there's a magnet in some cases. But they're designed for doing very high throughput analysis and very automated analysis of wine and juice. So you can figure out the exact composition, their provenance, where they're from, which country, which province or state or region. They can perform HDL, LDL, VLDL, lipid analysis as well automatically. And it's a walk away turnkey instrument.  In the case of mass spectrometry, there are kit companies like Biocrities, which will be co-sponsoring tomorrow's symposium. Shimadzu, which is also moving towards this. I believe A.B. Sykes also is trending towards this, where either the vendor or independent companies are selling kits for people to do, relatively automated high throughput quantitative metabolomics. There are also many regional centers, which allow you to just send your samples in and get your answers back. So the Metabolomics Innovation Center, TMIC, is an example. There are six regional centers in the US that allow that. There are regional centers appearing, or national centers in Japan and the UK and in Holland and in France. And then there are companies like Metabolon, also where you can take your samples, send it in and automatically, well, a week later, get your data back. So it does cost money, but there is a trend towards more and more automation. And if you tour some of these facilities, you'll see how they are trending towards automatic metabolomics. We've also seen an example of not just the equipment that's being automated, but also the software. So you guys had a chance to use Bazel, and you could see that it took a couple of minutes. But if you tried to do this manually, it would take all of you anywhere from half an hour to two hours to do some of the stuff with just a single spectrum. So having it work in two to three minutes and having it process 20, 30, or 40 spectra in a reasonable time and quite accurately is, I think, an important advance. We've also been working in the area of GC autofit. You guys have tried that. That's another example of automation. And again, most of you have given it a try. So it's not just the hardware. It's also the software. And it's happening not just in Tmic, the Metabolonics Innovation Center, but it's also happening in other places in North America and in Europe and in Japan where more software is being added. Now, there's still a bottleneck, as you guys saw, with trying to do untargeted metabolomics, but perhaps in a year, perhaps in two years, it'll be as automated as Bazel or GC autofit. I think that would be a really important advance. OK, so that's a little spiel about automated metabolomics. How about expanding metabolome coverage? So this is a picture we've seen before, and it's just sort of highlighting the number of metabolites or features that can be detected with different technologies and their sensitivity limits. So NMR, micromolar sensitivity, maybe about 100 compounds. DCMS, submicromolar sensitivity, maybe about 200 compounds. LCMS, nanosubnanomolar sensitivity, and thousands to tens of thousands of features. So obviously, if we can go to more sensitive instruments, we can cover more compounds, but the dilemma for us, and as you guys saw, is that many of the features that we see through LCMS methods are not identifiable.  We saw some features that were important. Some of them hit something. Some of them didn't hit something. And in most cases, 85, 95% of the time, the masses don't correspond to anything that are in our database. So the question is, what are these unknowns? And my belief, and I think a growing number of people are believing that these unknowns are actually metabolites of metabolites. These are transformation products of compounds that are already in our bodies or in plant bodies or other things, where other enzymes or other microbes or other processes are transforming and changing them into something else that is not common in other pathways. This is a picture that Augustin has been using in his lectures. It came from a paper that we wrote together about the food metabolome, or essentially exposures. And whether it's exposures that we get from our diet or exposures from drugs or exposures from pollutants, these all constitute either the pollutant metabolome, the drug metabolome, food metabolome, or the endogenous metabolome. And these are quite diverse. And the reason why they're diverse is that the compounds that are at the top are often ones that we already know. We have lists of all the known drug components. We have a pretty comprehensive list of all the chemical components in foods and the food additives. We also have a very comprehensive list of what are released into the environment in terms of chemicals, pollutants. But when these things go through microbial metabolism, house metabolism, whether they're digested or even if they're just processed through UV light or sitting on the water or microbes in the soil, they get transformed. And they get transformed into a green goop that we don't know about. And that's what we see with these increasingly sensitive instruments. So how can we actually characterize these things in order to be able to have continental identification in these compounds? We would have to have authentic standards for them. So whether it's 100,000 unknowns, 500,000 unknowns. And my own calculations suggest it could be up to 5 million unknown compounds. So to be able to synthesize 5 million compounds, to characterize 5 million compounds by NMR, to collect MS and GCMS spectra for 5 million compounds. That would cost anywhere between $5 and $10 billion. So the Human Genome Project was done for about $2 or $3 billion, and so these days no one's going to put that much money into sort of the chemical genome project. So what's the solution? If we can't get these authentic standards, if we're never going to have the chemical libraries, if we're never going to have the reference spectra, what should we do? So a task now, I think, is to move from trying to do it in the slow, tedious way of synthesizing and characterizing pure compounds for libraries to go to in silicoat metabolomics. And this is the idea of performing systematic spectral prediction for the compounds that we think exist or we know exist. So there's lots of compounds, but many of them don't have their spectral spectra collected. Many compounds that we know of at one time, but the spectra were collected 30 years ago and they haven't been updated, and so that's kind of useless. So this goes back to this concept of CFMID, but there's also programs like Metfrag and Metfusion. These are programs that can take a picture of a compound and predict the MSMS spectra or the EIMS spectra. There are also tools that we're working on to predict the NMR spectra of compounds in water, and there are also concerted efforts to try and predict the metabolism of compounds just from their starting components. So whether it's tools to predict spectra or tools to predict metabolites of metabolites, these are coming on stream fairly quickly, and these may in fact become the new reference materials for both the expected compounds as well as their expected reference spectra. So this will be, I think, an important way of expanding coverage of covering those unknown unknowns, of getting assignments to all those mystery peaks that Nama generated from her XMS analysis. We'll see. It may not yet work as we'd hoped, but it is already proving to be useful. There are a number of people that have been using spectral prediction methods to actually identify novel compounds, and there are a number of people who have been starting to use predicted transformations to confirm and also provide hypotheses for novel compounds. So that's, I think, another way of addressing the expanding bottleneck, expanding metabolism coverage bottleneck. The other one, I think, is very challenging for metabolomics. It's challenging for proteomics, it's challenging for genomics. It's expensive to do these things. You can't do it at home. You can't do it in the field. You have to bring samples back into an expensive lab that's very sterile. But one of the things that is happening is that people are moving more and more towards portable devices. So some of you might have Fitbits or have tried them. There are things called sensors and other kinds of tools that are like portable devices to monitor your health, can measure your blood pressure and body temperature, and they can even do some small chemical analyses. And so this concept of trying to democratize metabolomics to convert a 900 or GHz NMR instrument which would fill this room and two stories above us to something that you could hold in your hand is, I think, the best way of democratizing metabolomics. It's something that everyone could afford, everyone could do. It could be in every lab, it could be in the field, it could be in the farm. And so this idea of making a handheld system that could kind of scan up and down your body and tell you what's in you is actually not that absurd. So Qualcomm has just finished or wrapped up their XPRIZE for a tricorder. And it was actually awarded to a family firm in the U.S. and I think the Canadian group finished third in the XPRIZE competition to make essentially handheld medical devices that can measure or do a small amount of clinical chemistry but also measure things like heart rate, blood pressure, temperature, and other things. So, you know, if a family firm working in their basement can win a $5 million XPRIZE, it certainly suggests that the technology is starting to appear for doing miniaturizing of metabolomics. It's possible to do computer electrophoresis on a chip. It's possible to do HPLC on a chip. It's possible to do gas chromatography on a chip. And these are small chips and these are commercially available. It's also possible to get equivalent to electronic noses for small molecule detection. And these, too, are not much larger than a credit card machine. And they can, through various combinations of pattern recognition, distinguish between acetone, benzene, and chloroform. These are chemicals. They're volatile chemicals, but they are metabolites, if you want, or chemicals of utility for metabolomics. So, this is another trend towards miniaturizing chemical analysis. We've been working in Edmonton at the Metabolomics Innovation Center and with colleagues as well on trying to develop protein and RNA-DNA-aptum remediated metabolite sensing. And the concept here is to basically make use of proteins that bind metabolites specifically and to sort of carry out competitive binding assays. So, they're, in fact, whether they're paraplasmic binding proteins or antibodies, quite a number of proteins that are known to bind metabolites. Now, if you tag a metabolite with something like a gold nanoparticle or a fluorescent latex bead, you can actually carry out some kind of competitive assay. You can get compounds that bind, or if you've got the free compound, they can displace the gold nanoparticle from the protein. When you're working with gold, you can actually start doing a bunch of things with relatively low-cost sensors. You can use surface plasma and resonance, surface-enhanced Raman scattering, or you can look at electrical impedance because once the gold is displaced, these things change quite dramatically. So, if you've got proteins that are specific to metabolites and there's lots of them, then you can start making these kinds of handheld sensors. So, working with colleagues at the University of Alberta in electrical engineering, we've been developing this impedance-based metabolite sensor. And Reza has been involved with this work for a while. And so it uses either antibodies or paraplasmic binding proteins, conjugated metabolites, and a very, very small impedance sensor equipped with a very small inexpensive chip. The target is to be able to measure 8 to 10 metabolites at a time with different chips and to have the chips cost about $1 to $2 apiece. So, there are other people looking at miniaturizing metabolomics, but I think this is something that would make it much more accessible to a much wider community. Now, the other thing that I've been emphasizing, and I think some of you have started to appreciate, is the utility of having quantified data for metabolomics. Again, we tried to give you guys a flavor for untargeted metabolomics, which gives you relative quantitation or semi-relative quantification. We've given you GCMS and NMR metabolomics, which gave you absolute quantification. There's a cover of a Trends in Biotechnology article that was actually for the entire journal. It came about three years ago, and it had this title, a specter is hunting metabolomics, specter being ghost, specter of quantification. And two or three years ago at the time when this was published, more than 90% of the published metabolomic studies were basically semi-quantitative, people reporting relative peak areas, relative intensities. Less than 10% of the published metabolomic studies were using absolute quantification. Absolute quantification is key to reproducibility, and since this was published, a major crisis has appeared in all of science, which is the crisis of reproducibility. Most science is not reproducible. And the reason why is largely because people are not being careful with quantitation. They are not doing absolute quantitation. And the one or two fields where things are really reproducible is typically physics, where they're doing precise measurements of mass or the characterization of various leptons and bosons, where they have to be very precise. But in genetics and genomics and transcriptomics and proteomics, people are happy if they just get a set of values, which they report and only works in their lab. And if you go on any other platform, any other lab, you'll get a completely different set of values. Metabolomics has its origins in analytical chemistry and analytical chemistry, historically, was the most quantitative science in all of the fields of science. It was about reproducibility. It was about having standards. It was about reporting absolute concentrations in millimolar and micromolar and molar. It's also important that if you want to do practical applications in clinical work, in environmental work, environmental monitoring, in any form of veterinary work, what you report has to be reproducibly quantitative. So there are efforts with several companies. We've already mentioned Biocrities, Brooker. I've mentioned Canonomics, which is an Edmonton-based company. They've all moved towards quantitative tools for absolute quantitation. There's a number of academic efforts, whether it's things like Bazel and Batman and GC Auto Fit. You guys have tried a few of those. These are also trying to encourage people to do absolute quantitation. And when you compare metabolomics, actually, in terms of its record for quantification, it's actually not so bad. People have been characterizing serum and plasma. They've been characterizing cerebral spinal fluid. They've been characterizing urine for many, many years. And metabolomics, to date, has absolutely quantified, not relative, but absolute, about 200, almost 300 compounds in serum and plasma, 175 in CSF, about 400 compounds in urine. Now, metabolon can claim to have identified, I know, 1,200 compounds. But those are not absolutely quantified. They're relative quantifications. In terms of proteomics, a number of proteins fully quantified is now probably a little over 73. It's closer to about 100. In CSF, there's been 130 proteins fully identified and quantified in urine 63. In transcriptomics, because every measure, whether it's RNA-seq or microarray, is relative, there has actually never been fully quantitative data reported on genes. So, proteomics, which is 25 years old, genomics, transcriptomics, which is 20, 25 years old, and metabolomics, which is usually considered to be about 10 years old, given its late start, it's actually done remarkably well in terms of quantification. But a lot more could be done, because we know that in serum and plasma, there's probably 20,000 metabolites. In CSF, there's also probably 10,000. In urine, there could be 50 to 100,000 metabolites. So, we're only getting partial coverage. So, a lot more could be done, but a lot already has been done towards quantification. If more people were doing quantification, I think we'd do a lot better. So, quantification is a bottleneck that's being cleared, but not entirely. And I think another one that's really important in moving the ball forward is moving metabolomics from the lab to the clinic, or from the lab to practice. It doesn't have to be medical practices. It could be environmental. It could be in the area of veterinary science. It could be the area of plant science. In the case of clinical studies, a lot of them have focused on biomarkers. And over the last 45 years, there've been more than 700,000 biomarker studies or papers that have been published. But of those, fewer than 250 have actually been approved for clinical use. And that includes protein biomarkers, genetic biomarkers, metabolite biomarkers. Interestingly, with proteomics, there hasn't been a protein biomarker approved using mass spec. Almost all of them use ELISA's. There have been five biomarker tests that were used using gene chips or transcriptomics. But one of the things I think a lot of people aren't aware of is that if you're under the age of 25, you've probably had a metabolomic test. And we brought this up earlier, which is remarkable, given that it just doesn't get any traction. People don't mention metabolomics as being sort of the universal test that everyone has had. And I think I also gave you some of these statistics as well, which is metabolomics, even though it's a late comer, is moving into the clinic. And it's more so in the area of clinical chemistry. So if you tally up the total number of metabolites that are measured, at least in Canadian labs, and then are reported, it's a little over 320. If you tally up the total number of genes that are approved for genetic testing in Canada, it's about 130. If you look at the total number of protein tests that use ELISA, it's 108 that are approved in Canada. I've mentioned the gene chips, five. And then there was one proteomic test that was approved, but then it was moved to an ELISA. So it's back down to zero. So metabolomics is moving into the clinic because in fact, a lot of these tests are relatively quantitative. And that's been what's held back transcriptomics. It's what's held back proteomics. In ELISA's, the assays are relatively quantitative. And in genomics, it doesn't necessarily have to be quantification. It's simply say the mutation is an A to a T or a G to a C. And so it's important or not important. But that too, you could say is reasonably quantitative. But given the relatively small investment that's gone on to metabolomics, which is actually less than 1% of the investment that's gone into genomics, and less than 5% to the investment that's gone into proteomics, metabolomics has actually done pretty well. So not only for a small amount of money, but for a relatively short period of time, it's actually made those translation to clinical practice quite well. If we're looking at biomarkers, you can sort of compare how metabolomics does to some of the other methods, but also just in terms of certain conditions to explore. So you guys were working a little bit today with data that we'd had from preeclampsia, looking at mothers at three months into their pregnancy, and then looking to see if we could predict which mothers would actually have preeclampsia later on. And using metabolomics, we saw we were able to get an area under the curve of about 0.94 to 0.96. So that's an example of preeclampsia. You can also do the same for late preeclampsia, looking at serum metabolites. You can get areas under the curve, rock curves for diagnosing heart defects, gain well above 90%. You can even do sort of genetic testing for an infant's three months into gestation to identify which ones have trisomy 21 or trisomy 18. So this is typically before you can do amniocentesis, and this is just simply looking at metabolites. We also had an example where you guys were looking at catexia of people with colon cancer and lung cancer, and when you use that data, it's also possible to get rock curves that are above 80, 85% in terms of predicting which individuals will develop catexia. So if you can predict when people might get a disease, then often you can prevent it. So in the case of preeclampsia, a very simple preventative treatment is to use aspirin. In the case of catexia, changes in terms of dietary consumption of certain fatty acids and certain amino acids also seems to slow it down or prevent it. In terms of diagnosing diseases, metabolomics also is a very good tool. These are some examples again from the team at Group in Edmonton where we've looked at using urine samples to diagnose kidney rejection.  So it's pretty painful and it happens a lot, especially right after treatment or if there's been a difficult bout of certain disease. So if you could just have people have a urine sample and determine whether there's a rejection happening, then again, it's easy to diagnose and actually easy to treat.  Works well for pediatric cases. Also seems to work well with heart failure. There seems to be some metabolic tendencies that have been seen not only by our group but other groups in Australia to diagnose chronic fatigue syndrome, which is very hard to identify. Eosinophilic esophagitis, another one that seems to be diagnosing quite well. And one that we, I guess, are quite proud of, this is involving operations with a company in Edmonton called Botanbolomics Technologies Incorporated. They developed an NMR assay to take urine samples and to distinguish people who have colonic polyps from those that don't. So polyps are the precursors to colon cancer. And currently the best way to characterize whether someone has colon cancer or polyps is to have a colonoscopy. And if you've ever known anyone who's had one or if you've had one yourself, they are rather painful and they're also quite elaborate. So you're basically out of commission for about two days. You have to change your diet before the colonoscopy. You also have to recover for about a day or more after the colonoscopy. And if all gastroenterologists have their way, everyone would have a colonoscopy every two weeks sort of thing. So obviously it's too expensive to do that. Obviously, I mean, the typical colonoscopy is about five or $600 in Canada and the US, it's maybe a thousand. It's a money maker, but that's not exactly how health systems want to work. If you can have just a simple urine test that could pick up the polyps or at least screen the people who seem to likely have the polyps, then it'd be a whole lot cheaper. So we worked with them to convert the urine test which used 12 metabolites to a mass spectrometry-based test that uses three metabolites. That was successfully done. And because it's using multiple metabolites, we can adjust the sensitivity and specificity of the test. So it's now been picked up by several companies in the US which are now using it to screen patients for colonoscopies or not. So this is one of the first examples of a multi-metabolite marker moving into the clinic. Now, those are some trends. We've talked about automation, expanding metabolite coverage, making metabolomics more portable, efforts to quantify moving metabolomics and allow them to clinic. So some of these things are starting to happen. They're trying to give you some examples, but more needs to happen. And I think another area where more needs to happen is trying to get metabolomics into drug discovery and development. The history of metabolomics is that it was first used in drug discovery and development. It started in Imperial College and it was a pitch to drug companies. But relatively quickly, they decided to abandon metabolomics. It was called metabolomics back then, partly because it wasn't quantitative, partly because it wasn't portable, partly because it didn't cover things and partly because it wasn't automated. So now that we're getting closer to automation, expanding the coverage, making things a little cheaper or more portable, but we're quantifying. And there are clear examples of where metabolomics has now moved from the lab and the clinic. I think it's time for the drug companies to start thinking seriously about metabolomics. So if you look at drug discovery and drug development, the cost and time to take a drug from concept to final product is about 10 to 12 years and anywhere from 800 million to $1.2 billion. Interestingly, there are different phases where drug technologies are needed. So the first phase is discovery, typically chemistry's involved. Discovery in phase one analyses is often worked with genomics and proteomics. But in fact, metabolomics is needed just about every phase of the drug development process. And this is illustrated here. So in many cases, people are finding drugs. Through metabolomics, they're finding drug targets. And in some cases, they're finding natural products that seem to be effective in fighting or in some cases causing disease. So once you've got a drug lead identified to metabolomics, then you can also use some of the automation that's been developed to identify toxicity for the drug. So that's can be done on mice and rats. And then there can also metabolomics can be used to assess efficacy biomarkers. So you think the drug is working, well, let's see if it actually changes things. And so you can start looking and using metabolomics to find these efficacy markers. Then you can also use metabolomics to assess preclinical safety or to look at toxicology, particularly as you move from animals to humans. And then as you move to later phases in the drug development, you'll look at clinical safety and clinical efficacy markers. So an example of this would be here where generally when you do clinical trials in phase two and phase three, you recruit a bunch of people and you tell them, take these drugs, but do not take them with alcohol. And everyone will come and say, yeah, I didn't take any alcohol and I've taken the drugs. And then they'll analyze people and they say, well, obviously you didn't get any better or there isn't any response or you're sicker now. And they're stumped. But if they could actually analyze people's blood or urine and to look for things, you could actually see in this case, this person, even though they said they didn't take alcohol, they did. And so this is a way of monitoring compliance for clinical trial patients. Then it's often a case that just one or two outliers in a clinical trial can destroy a billion dollar drug effort. You can also look at individuals in these clinical trials to figure out whether people are slow metabolizers or fast metabolizers. Some people will take drugs and will metabolize them very, very quickly. And in fact, it seems like the drug has no effect. I am a rapid metabolizer of caffeine. So if I try and drink a lot of Coke and coffee right before bed, I will promptly fall asleep. Our other people, I imagine, are slow metabolizers and in fact, a cup of coffee even at four in the afternoon will keep them up all night. So this is something that differs with individuals and it's very much a function of their physiology as well as their genetics. But you can't predict purely from genetics and you can't predict purely from physiology. The best way to see this is through metabolomics. In terms of traditional drug discovery, there's a model that's been developed and used probably the last 10 or 15 years. A lot of techniques are based on doing large scale studies sometimes with genome-wide association studies or GWAS. The idea was to hopefully identify genetic variants that were seeming to cause certain disorders. In many cases, only 10% of disorders or disease actually have a genetic basis or a clear one. So typically the GWAS studies are only leading to about a one in five or one in 10 success rates. They're big, they involve tens of thousands of people so they cost millions of dollars and they often take multiple years. Once they found potentially target gene, then that gene has to be drug-able. In some cases the gene is not drug-able and even if the gene is drug-able then the protein target is not amenable for drug-ing. So usually they lose about half to the drug-ability issue or half to the protein issue. So once they finally isolated the protein target that they want to drug, then they start doing high throughput screening. And the typical success rate for that is about one in five of the protein targets they put into their system leads to potentially high nanomolar affinity drug. One in five success, that screening process can take anywhere from one to five years. But then to take that drug lead and actually try and get it into phase one, preclinical phase two trials, that's where it costs a billion dollars, that's where it costs or takes 10 to 15 years and that's where the actual ultimate success is only one in 500. Once the drug is formally approved, there's about a one, well maybe it's not quite 50% but a reasonably high probability that in fact the drug will be taken off the market because it has or proves to be ineffective or too toxic. So even approved drugs are regularly pulled. So if you add the one in five, one in two or multiply one in two, one in two, one in five, one in 500, one in two, you end up with essentially from a beginning GWAS study to the point where you have a final product of 0.001% of getting a drug to the market. It's gonna take 20 years and cost more than a billion dollars. That's largely why many drug companies have stopped their drug research. It's also why really all we're seeing now are copycat drugs coming from pharma companies or why we're seeing a lot of drug companies merging with each other because they can't sustain this. On the other hand, you could think of trying to use metabolite-based drug discovery. So metabolite-wide association studies, MWAS, actually can be done with a much smaller cohort because metabolites are the canaries of the genome. They're more sensitive. So you can actually do a pretty decent metabolomic study for a couple of hundred thousand dollars. And in our case and I think in many other labs, people have found very good and very useful markers but also probable targets that suggest that if this metabolite is reduced or if this one is increased or if this protein is made so it could increase these levels of metabolite, there would be a positive response. You guys have seen some of how quick it is possible to analyze your data, your metabolomics data. You did it this afternoon. So whether it's a few hours to a few days, you've also done some pathway analyses which help identify some of the proteins or pathways you want to target. You can use some of the databases we've talked about to learn a little bit more about those pathways and processes. And in many cases, if it's a case that there's a shortage of a metabolite or in other cases there's an excess of a metabolite, it's possible to simply substitute for that compound or to find certain types of proteins or enzymes that may modify that metabolite level. If you're wanting to see whether this is actually making a difference, then you can do metabolomics to monitor. So in these cases, it's possible to go from 15 to 20 years and a billion dollars to do something where you've got a possible or probable compound that's maybe even being used in the clinic in less than a couple of years and having excess sex rates of about 15%. And as I said, we've done this with colonic polyps and it's also suggested some other routes for treating a couple of disorders that we've been working on. And there's been some really interesting examples elsewhere, not just in our labs, but in Stan Hazen's group. So this is an interesting story. And they screwed out of the Cleveland Clinic with work that they were looking at with people who exhibited heart disease and atherosclerosis. And it's generally well known that people who have atherosclerosis typically have had high fat diets. They've all their lives, typically they're obese, typically they have a record of consuming fatty foods, lots of cheese, egg, and meat. But not everyone develops that. And there are actually large populations that have very fatty diets but have very low levels of cardiovascular disease. And in particular, over the last 30 or 40 years, people have been very interested in the incidence of heart disease in France and Italy, Spain, and other countries where consumption of eggs, milk, cheese is very high. And total fat consumption is much higher than in many other countries, but cardiovascular disease is very low. So why is it that some people are able to avoid heart disease or atherosclerosis and others, particularly in North America, seem to have high levels of cardiovascular disease? So what they found was that with people with atherosclerosis, they had high levels of trimethylamine oxide in their blood. Now TMAO is also something that you'll find in urine at fairly high levels if you eat fish. So it's a marker of fish. But normally it doesn't persist for long in the blood. And so they found these persistently high levels of TMAO and about 2011 was when they first reported it and they've reproduced this in multiple studies. We've also seen it in others. And then they tried to go back and look at these pathways and to try and understand it. So here's the lead, what's it meaning? So they traced it back and said, well, trimethylamine actually comes back from trimethylamine, trimethylamine oxide. So trimethylamine is a precursor for trimethylamine oxide. Trimethylamine oxide, TMAO is produced in the liver but trimethylamine is produced in the gut. Where does trimethylamine come from? Well, it generally comes from choline or other tertiary amines, which are generally produced from fatty foods, phosphatidylcholine. So here you've got an interesting link between what you eat, what's in your gut, which converts the phosphatidylcholine to choline to trimethylamine, and then what your liver does. So they started out this pathway relatively quickly, just like you guys would do from keg or HMDB or SNPDB. And then they said, okay, where should our drug target be? Well, should we target the liver so it doesn't convert TMA to TMAO? Or should we target the microflora so it doesn't convert choline to TMA? Or should we target people's diets and just tell them to stop eating fats? So the fat drug didn't work, and then they tried the liver drug and that proved to be too toxic. And then they said, well, let's try and look at the bacteria and see if we can change that. So in 2012, the other group started characterizing a particular enzyme that's found only in sulfate-reducing bacteria. And these bacteria are not in everyone, although they tend to be relatively high abundance in people in North America. And the enzyme that's produced by these bacteria is called choline TMA liase. So it converts choline into trimethylamine. So if you have these bacteria in your gut, you will tend to have high levels of TMA. If you don't have these bacteria in your gut, you will not have high levels of TMA. So then they said, well, now we've got our drug target. Can we start screening it to see if we can find compounds that stop TMA liase? So they started dumping all kinds of different things on them, and one of the things they found that really worked very well at stopping TMA liase is something called 3-3-dimethylbutanol. So these are the structures. So there's choline above and there's 3-3-dimethylbutanol. It looks a lot like choline. So in fact, it's a very good inhibitor. So where do you find 3-3-dimethylbutanol? Find a lot of it in extra virgin olive oil, in grapes and in red wine, which are sort of the characteristic features of the Mediterranean diet, which is what you eat a lot of when you're in Italy and France and Spain. And so it seems to have a really interesting effect or potential where A, here's metabolomics, finding a marker, B, identifying a pathway, C, identifying a drug target, D, identifying a potential inhibitor, and then finally pointing out to a rationale why certain populations have relatively low heart disease and why other populations have relatively high levels. So with that, I think I'll wrap up here, but what I've tried to identify are some of the bottlenecks that are limiting metabolomics, the lack of automation, relatively limited coverage, the fact that it's expensive to get into, the fact that historically it's been non-quantitative, the fact that it hasn't really moved from the clinic or at least we didn't know it was moving from the lab to the clinic, and then the potential or the limit applications metabolomics to drug development and discovery. What I've then tried to do I think is then identify areas where in fact it is happening, where you are seeing automated metabolomics, where you are seeing expanded coverage, where you are seeing metabolomics becoming more portable or quantifiable, and where there are plenty of examples of metabolomics going from the lab to the clinic, and where there are nice examples of how metabolomics is helping with drug discovery. And so what I'm hoping is that you could be messengers that in fact metabolomics is not sort of this obscure science that's leading nowhere. And in many respects, in fact, it's probably more automatic than many other omics methods. It's moving more rapidly, expanding more rapidly, that it is the most quantitative form of omics technology, that it is already successfully translated to the clinic over and over and over again, more so than any other omics field, and that it is happening I think the significant impact in the field of drug discovery and development. So be happy that you're actually in the field of metabolomics or that you're interested in. I think it's a burgeoning field and it could take you a long ways if you want to stick with it. So with that, I think we'll wrap up the course and I'll thank everyone for listening in, attending and working really, really hard.


Good morning everyone. I'm Pranjil Sharma. Welcome to this exciting session on economic integration of South Asia. Before I say anything, let me quickly introduce our panellist, Minister Mustafa Kamal, Minister of Planning from Bangladesh, Minister Malik Samaravikrama, Minister of Development and Strategies and International Trade from Sri Lanka. Richard Rekhi, Chief Executive Officer and Managing Partner of KPMG. Siddharj Azmat Chaudhary, Chairman of Cargill India. And Dr. Sameer Saran, Vice President of the Observer Research Foundation. This is a very interesting conversation and I'm sure you realize it's happening at a very crucial moment for South Asia as well. South Asia has been traditionally fragmented in every way that you look at it. Politically, security-wise, economically. And now I think there is a realization across the region that it should not remain like this. We have seen far more disparate regions come together. East Africa has a customs union. South Asia has a great example for us. So what can be done to ensure that South Asia is and should become a far more cohesive market where the trade and investment links can be enhanced. I'm going to request all the panelists to share their views and of course their experiences and ideas on what should happen and what has happened so far. Let me begin by requesting Minister Samaravikrama to give his perspective. Sri Lanka in many ways has shown the way for South Asia in terms of economic growth. You have, despite the past, a very stable economy. Minister, what is your view on how can Sri Lanka and the other countries come closer? Thank you. Morning everybody. First of all, I think we must understand that this historical circumstances under which South Asian countries were born and the resulting identities they carry don't make cooperation easy. Most of the countries are still preoccupied with the internal consolidation to invest political capital in regional cooperation or regional integration. There's also a lack of state capacity that has been a factor and at the same time there are series of groups with vested interests that continue to benefit from political conflict, political economy of conflict and the status quo. So that is the background that our countries were born and we have to really seriously think of how we can go forward. Having said that, there are many opportunities I can see. There have been at least at the official level and political level, at the leadership level, greater readiness to accept the need for regional cooperation. You know, yesterday our Prime Minister and Prime Minister Narendra Modi had very cordial and extensive discussions on how we can work together. So there are also major projects underway, particularly in the northeast of the subcontinent where we see connected between Bangladesh, Bhutan, Nepal, India is significantly enhanced. In addition, from Sri Lanka's point of view, we have a free trade agreement with India and now we are in the process of deepening that agreement and we are looking at a more comprehensive economic and technological cooperation agreement which we hope to have in place in the first quarter of next year. At the same time, we are invigorating the free trade agreement we have with Pakistan. So from our point of view, we are looking at a market of about 1.5 billion people. So I think this is, I believe, the way to go forward. Right. I'll come back to you more on how Sri Lanka and what is its footprint across South Asia and how do you see the next step. But Minister Kamal from Bangladesh, you have again a very special place in global trade with very clear focus on industries like textile. Where is Bangladesh and its integration with the other countries in the region? Okay. Good morning to everybody. This is, as you are aware, Bangladesh is a country. If you don't visit and don't know intensely in that case, you will not be believing. So that is the reason that World Bank President, he himself is coming on the 14th to know himself, the incredible growth Bangladesh is having. I'll give you a few points. You see, just 10 years back in the 2005, we had a poverty level to the tune of 43%. In 10 years time, by the end of 2015, it has come down to the level of 11.1%. So that is amazing. It's simply amazing. And this, in the country, it has endured a lot of gifted endowments, as you are aware. 76% of our 160 million people are of the working age population. And this demographic dividend, we shall be achieving until 2045. Now, another leadership of our, on our five, Mr. Shaikh Hassanah, she is a visionary leader. She works by numbers, objective based. And that is the reason, during the last seven years, we have been, we have been consistently far performing over 6% of the GDP growth. So the average GDP growth is 6.3% during the last seven years, eight years, time. Last year, we have achieved 7.1%. This year, we have a target to achieve 7.25%. As per our projection, by the year 2020, we shall be achieving seven, seven, eight percent. And this eight percent, we will continue to achieve until 2030. You might be knowing, Fiaswara and Cooper's and Goldman Sachs, everybody has projected that Bangladesh is one of the countries. There will be never growing less than 6% until 2050. Unbelievable. So based on that projection, by the year 2040, they have indicated Bangladesh will be 23rd largest economy in the world. But as a planning minister, I shall be sincerely pursuing my endeavor so that now, you know, when the 2020 meeting is there, in that case, Bangladesh is also being invited from the sidelines. But my endeavor will be, we want to be on the main frame by the year 2040. This is our, one over five minister also has projected like that. We should be, we must be joining the big countries, elite countries, like India. India, India right at the moment, it is seventh largest economy in the world, as you are aware. But one thing I must, I should tell here the, I'm grateful to all of you because you are here for one cause that causes to serve humanity. And I also as a minister, I work in Bangladesh for the cause of humanity to make improvements in every areas of economy so that people can stand on their own feet, can, I can have everybody on the main stage of economy. Now you see, last 500 years, it was the time for the West. Now, next 500 years will be the time for the East. But you know, there is no denying to this fact. I'm just, I just, just one minute. I'll take one more minute. Because what I am saying, it is a, it is from history. Exactly in the year 001, 2000, 2016 years back, India was number one country in the world. And China was number second, number two country in the world. China at that time was having one, one-third of the population and one-third of the world economy. And China was having one-fourth of the population and one-fourth of the economy. Even you might be knowing when East India Company was formed in, to the, in 1601, exactly on that day, India was occupying 22% of the world economy. So what you had, you are trying to go back to that, you know, because there is a, there is a, there is a transformation everywhere. So my idea is this, if India grows, if China grows, they can't grow themselves alone. They'll have to take, Sri Lanka and Bangladesh also along with them. So this is my, this is my objective of talking so much about India, because you have not offered me cup of coffee. But even then I have said, I'm saying for my sake, again I'm saying we'll have to integrate ourselves, we'll have to, we'll have to move forward together and we'll have to move as fast as possible. I think I agree with you because you said, you know, we have another 500 years. I don't think we have the patience for that anymore, because we are one of the most populous regions in the world. I already started, I'm saying, you know, because you should not even, you know, by the year 2013, not by that, no, I see already China is number one in terms of purchasing power purity. So by the year 2040, China will be number one country in terms of purchasing power purity, as well as in terms of nominal, nominal value basis. And at that time India will be number two and America will be number three. And if anybody is from America, don't, should not be upset. You know, at one time, even Argentina was number one country. So only exactly in the year 1892, America became number one. So before that others were number one. So we want to get back to, get back to our own position, old position by pursuing our, and by exploiting our resources. That's a great point. So let me bring in Siraj here. Siraj, as, as an investor, you have to put the money on the policies that are announced. As a global corporation, also with the South Asia footprint, tell us how do, how do you see the region? Is there, is there a common market for you already? Do you see that as an aspiration which is too far to achieve or is it closer than we realize? Thanks, Pranjal. I think to begin with, I would say that, you know, we, the numbers are all there to say that there is an opportunity. I mean, there's broad consensus that this is a large population spread across this region. You know, one of the fastest or the fastest growing GDP. The demographics are right. So in theory, everything looks good. I mean, any corporation would look at that population, would look at that, you know, demand, the GDP rate and, you know, the growth rates that are happening. But there are challenges.  So India obviously is in the forefront, probably because we started earlier and having the advantage of the large population, land mass education, whatever you call it. And then leveraging the presence in India to spread to the neighboring countries is, I think, the approach a lot of corporations would be taking. We've been looking at the same thing, particularly being in the food and agriculture space that provides us an opportunity. But to say that have, I mean, are things great? The answer is no. Are things better than they were in the past? Yes, certainly. I mean, we are finding opportunities to get across the border to supply food, to, you know, get into processing. And so there is that change happening. So in my view, I think we have some distance to cover. What would you like to be changed, Raj? I think it's a lot about the internal processes. And to be fair, I think each of these countries, I mean, first have to get their own house in order. I mean, to say that it's, you know, ease of doing business in India isn't great for companies in India as yet, right? So to suddenly expect it to be great for people coming from outside. India has been 29 markets, so finally we'll be one. Exactly. So I think everyone has to, I mean, the phrase I was sharing with you before this thing was that, you know, you can be nice to your neighbors if you're happy in your own house first. And I think that's the stage we are in. The good news is that we're all getting happier in our own house. And therefore, there has to be optimism that going forward, there will be more and better collaboration with the neighbors. I think what we've started doing, we've now, we have more comfortable being counterparties to each other. I think that's the first step towards becoming partners to each other. I think that happiness must spread, as you're saying. And hopefully, the happiness spreads with more money being, you know, traded and more well-being shared across the region. I mean, I can actually add sort of an example, which is not business, but that has kind of worked well for the region. And that's totally different from what we're talking about here. That's actually cricket. I was wondering when this word would come up. And if you see the evolution of cricket, I mean, we were individually the whipping boys at different stages of the evolution of world cricket. And over the years, as one country and the other country gained experience and became better, our ability to support each other in the ICC, our teams doing better. And with the result and with India being the center, the region has been able to hold so many world cups together. Individually, Bangladesh, Sri Lanka or Pakistan would not have been able to hold a world cup. But together, we've been able to bring that change. And I think with that, the economy and the IPL now where everyone plays as part of the same team. So that's really a symbolic indicator of how things can move as each country sort of strengthens its own. That's a good example and symbol of cultural affinity, which needs to be built on. Richard, you advise global corporations who are investing in India and the region, and you're also advising regional global companies. Are people ready to look at South Asia as a region or are investors still looking at each country as a separate market and then therefore having to navigate across each country rather than looking at one region? So like Siraj said, I think before I answer that question, I think it's important to understand that this region, South Asia is possibly the fastest growing region in the world today. In terms of GDP growth percentage, I think it'll be about 7.3 if you take the whole region together. And with Minister just said that they've got projections to go up to 8%. So all that will add and further enhance the growth in the region. So the second one, which I would say is that this total region has an economic value of about 2.5 trillion dollars. And once we are a region of 2.5 trillion, it becomes a big, you know, you go for bargaining on any trade agreement on every such thing, it becomes very useful. And if you take Bangladesh, which is there as the bridge to connect South Asia with Southeast Asia and become that link, I think you are creating a completely very different trade barrier. So you've got a 2.5 trillion economy, South Asia trading with another 2.5 trillion economy, which is Southeast Asia, the ASEAN region. And imagine what trade can be done because once trade comes together, it builds prosperity. Prosperity will build peace and bring harmony in the region. And each of the people will each of the countries will actually develop out there. I think even we go down further and look at which areas would look at it. You take Sri Lanka. Sri Lanka has the maximum accountants per capita, accountants per capita anywhere in the world. I think it is the number one. If you take India's accounting base, we can become the accounting powerhouse and we can build the KPOs, the BPOs, the back office in this region and it can become a very large thing to the world. So this is one area which one can definitely look at as a as a big advantage that we could look at. And the other one could be when we look at the trading on the past side, if you look at between Bhutan, Nepal has got those Heidel kind of how do you get it? Bangladesh has got gas. How do we actually get that gas transported? So the point is there would be more economic efficiencies. More economic efficiencies, better price to the consumers. Today if you see because we are disjointed economies and with India now bringing GST in and becoming one market, I think India is now ready to take the next leap. And India can play that one role of saying, okay, how do you actually unify this market and take it to the next level? So I think there is a good sense in my view of looking at South Asia's one market. When you talk of global companies, when they look at they still don't look at it as South Asia, honestly, they will still even when they look at India, they look at which state they want to come in. So they don't look at India as India look at which state they come in, they put their industry. But when they come into India, then they say, okay, why are we missing these markets? Then they move into Bangladesh and Sri Lanka as markets which are there. And both these markets, for example, we do a lot of work in Bangladesh out of India. So we have seen that market little more closely. Fortunately, I've traveled to both Sri Lanka and Bangladesh and understand those markets. And we have we have been doing a lot of advisory work for clients out there. So textiles is another thing which can actually bind it. And if you look at textiles, textiles is possible because you have created your experience. Do you see companies in these countries working closer with each other now? Yeah, you will find I mean, there are a few examples of people from both sides where Bangladesh companies have come into India, Sri Lankan companies have come into India, Indian companies have gone into these regions and they are trying to collaborate and work together. Because they find that, see, because you can't ignore this market. You see the Indian market today has encouraged Chinese goods to come in. So why don't we let the South Asian goods come into this country? I mean, simple. I'm just saying look at that as a area of which one could look at. That's a great point. Sameer, it looks like from all the speakers that a lot of individual and independent efforts are happening. We've had structures like SARC and BIMstake and some others. But it seems that those regional frameworks have not perhaps been as efficient.  So I ask you the simplest question. Is SARC dead and should we move to a new way of doing business with each other? Is SARC dead? SARC in some of that will continue to live. And I think the efforts to create smaller subregionals is in a sense the beginning of the revitalization of SARC. I believe if we can get five or six countries working together, that might attract even the others to join in. So I think to keep SARC alive, we need to get the BIMstake working. We need to get the B of Bengal community vibrant. We need to get the BBIN grouping, make it feasible, make it efficient. But I think let me make three points and let me also confess that I was drafted last minute and I was told that you need to be here because you don't know anything on trade. So we need someone who looks from outside. So let me just make three or four quick points. The first is I don't think regional integration is anymore an option for India and its neighbors. I think it is a compulsion. And let me tell you why. I think the fundamental assumptions of the past century, where we all believe that the open, free, liberal trading order, the global trading order would allow us to grow and benefit from international markets' consumption is over. Those who created the international trading system are undermining it. The WTO framework is waning and is a pale shadow of what it is meant to be, which clearly means that new arrangements are being crafted even as we speak. And in that sense, countries who require 20 years of unhindered growth will have to find new arrangements for themselves, even as the Americans stitch together various treaties and our other neighbors create their own arrangements, one belt, one road and others. Smaller countries will also have to find markets, will also have to find new trading deals. So I think it's a compulsion today. It is no longer a luxury. Second, I think the assumptions, some of the other assumptions are also dying. So manufacturing led growth, for example. That assumption, I think China was the last country which moved from low-income to mid-income or low-mid-income using this particular assumption. It's not going to be valid for many of us who are growing now. Which means we will have to first invest in niche manufacturing. Two, we will have to invest in services and the knowledge industry that my fellow panelists was talking about. And three, we will have to invest in regional value chains. We cannot compete unless we can understand the power of creating value across a region. And let me give you a simple point. Most of our countries have industrial policies. All of our countries on this particular panel have industrial policies that are primarily drafted to drive exports up, not to invest in regional value. All that we are wanting, all that our countries demand is that somehow we produce large volumes and export it to our neighbors and export it to other markets. We are still not thinking strategically to that how can a steel industry have components across the Bay of Bengal community? How can a digital company see value across the waters of Bay of Bengal? And I think that's one point we have to start. Right. And let me give you the last point. I think India is to blame for this region. I mean, I'm being very clear. I think we have not done enough as the largest market in this region to promote regional connectivity. And I think there are two reasons for this. One was our obsession or fascination of being a continental actor. We like the land more than water, which meant that we were always looking to our West. That was one reason. The second, of course, was the fascination with the fossil fuel economy. That because oil resided in the Gulf and in the West Asia, we were always looking for linkages to that part of the world. We ignored our East for the longest time. And we were we were afraid to get getting our feet wet. I think that is changing. So as India sees itself emerge as a maritime actor, I can sense the importance of the Bay of Bengal community thriving. And finally, in the short term, physical linkages may still be important, but believe you me in the long term, and when I say long term, I mean 15 years time and not that long. Digital connections will be all that matter. Geography will be irrelevant. So if we can create a digital economy, a digital Bay of Bengal, a digital BIMS tech, a digital South Asia, we will not have to worry about cross border trade and transit points and check points and surgical strikes. I think we can get into the business of doing business. That's that's that's important to understand. But you you the question I raised to you, I'm going to raise to both the ministers as well. Ministers, Samal Vikrama, Sark has not delivered. And we're looking at something like a Sark minus Pakistan, at least on the trade and economy front, because you can't be held up. You have to move on. So and the regions, as as Samir said, there is a compulsion for the countries to work together. What are the structures you see that can help bring the countries and the economies closer and be more integrated? Do we have to look at a new framework? Or do we have to reform the existing frameworks? Yes, now actually, I'm for total economic integration in the region in South Asia. But the fact is that it's it's natural for neighboring countries to trade more with each other. But if you look at South Asia, our trade is just inter regional trade, accounts for less than 5% of total trade. And inter regional FDI is a mere 4% and that too most of the inflows have been from India. So this shows that we are nowhere near where we want to be. And of course, there are many obstacles which have been there, high cost of trading within the region, absence of regional value chains, complicated and non transparent. But so what will get everybody to sit together under one group to get this? First of all, I think it is extremely important to have for India and Pakistan, the two largest economies in the region to find a way of working together. So are you saying that unless India and Pakistan economic trade picks up, the rest of the countries cannot work with each other? I'm not saying that now individually, we have all these countries, Bangladesh, Sri Lanka, Pakistan, India were shown reasonable growth. But if you're looking at regional economic cooperation, which can really boost all our economies, then India and Pakistan have to be together. I work together, we must find a way of working together. I don't think any country needs to have the veto over integration. So I don't think if we begin with this notion that everyone has to be on board, and then we will create a framework, it's going to work. I think we can clearly begin on a sub-regional level. We can talk about a common trading platform amongst four or five or six countries, and I'm sure that power of that platform will attract the others in. So I don't think we should allow either India or Pakistan to have veto over regional integration. Mr. Kamal, would you agree with what Samir is saying? You see, the forum today, it is economic integration. Economic integration in the Southeast Asian countries. Now, I think it is a premature idea to exclude somebody. You see, first of all, I think with the passage of time, everybody will understand, even Pakistan cannot remain isolated, or one of them can't remain isolated, or India also can't remain isolated. So from an economic perspective, I think we should have a still scope to revisit the whole issue. But do you think, sir, we need a new framework for economic integration? I think framework we have. The framework we have, it is not workable. It has become defunct. What can you do to make it work? Since inception, it has become defunct. What do we do to make it work? What His Excellency Sri Lanka has suggested, you see, first of all, you have to sit together. See, the smaller groups, say, let Pakistan and Afghanistan sit together. They find out some communities and then let Maldives be included. Let Sri Lanka be included.  You can just don't give it up. I think we should still have a chance to work together. And if at the end of the day, end of the day, is not working, in that case, you can have a decision. But you have been stuck. You have other options as well. So those options should be strengthened. Those options also should be strengthened side by side. You see, one thing is very, very clear. Our this community is very fragmented because still we are not working in close harmony with each other. Still, either disrespect or the methodology we have not fixed up, how we can maximize our resources, how can maximize our benefits. You see, in the north-eastern part of India, there is a possibility of 80,000 megawatt of electricity could be produced from hydro. Same quantum could be produced from Nepal. Even 23,000 from Bhutan. Have we ever tried? Have we ever even exploited? So such huge resources at our disposal and it is green energy, which is the solution. By the year 2030, you'll have to go for green energy. So I think these sort of resources should be exploited. And then I think slowly, gradually, things will be definitely coming to a proper shape. Anybody, China alone, how they can become rich, how they can become number one without, I mean, living the neighbors isolated, not at all. So even China, India, Sri Lanka, I mean, our, this group, as Mr. Choudhury has said, he has said this, I think, seeing me in the, in the, in the, here, you know, he was talking about, he was, he was talking about cricket, you know. The cricket is not today's subject, but you are talking cricket because after seeing me, you know that I was, you know that I was the president of ICC. And one thing is very clear. I should tell you in our country, if you ask people, there are many religions. There are Buddhism, there are Muslims, there are Christianities, there are Hindus. Okay, fine. So they're subdivided and fragmented, but there is only one religion that is about cricket. So cricket is a religion there. So through cricket also, I think we can develop our friendship, develop our bondage, and this way also, we can touch each other's mind and we can touch each other's hearts and we can win over everything.  And if we go back to those histories in that case, we'll have to agree that we have also possibilities of moving forward. So you write and I think Siraj is right that cricket is binding us. Only one thing, one point I will take from, I will explain you. Now I'm talking here as a minister, but I'm from business background.  I also work with KPMG. Now, about Bangladesh, I'm telling you, at one point of time, I was employing over 6,000 people. I never sustained losses. In Bangladesh, if you invest money there, it is open. In any sector, you can invest other than, other than defense. Only one sector is earmarked, kept outside the far view. That is defense. In any sector, all sectors are open to everybody. You can invest even 100%. That is the only one, that is the country. If you invest money in a factory, in that case, automatically you become the owner of the land itself, free old land. It's not a, it is not a leisure land, things like that. And in Bangladesh, if you want to, if you invest money, if you wish to incur losses, you have to make a plan. If you want to make profit, you never to make any plan. Because safety net is so big, you can take it from me. Because I had over 6,000 people and I started my, I started my, initially I started from business. So I know what it offers. Great. So let me bring in Siraj here.  Cricket has made a lot of money for itself, but it has to make money for other sectors as well. It's not making money. It is integrating people, touching each other's, touching each other's minds and hearts and winning people, engaging them, engaging them, the main course. Using that to bring better business ties, I think that is still missing. But Siraj, the concrete steps like the Bhutan-Bangladesh-India-Nepal road project is something which is something on the ground. It's for the first of the trucks have moved and crossed borders and brought in the test pilot stage. How important is that for the region, especially for a company like yours? See, you know, going back to the point that has been discussed here, saying that, okay, there are a lot of differences within the countries. I mean, despite the similarities. So one approach could be to say that, okay, because we are neighbors, we ought to be together. So that's a sort of broad statement saying that that's the logic. But there are realities which don't let that happen. So then we have to go into finding areas of interdependencies.  And I think this, the BBIN or the CESAC, CESAC, which is more a project driven approach, those are beginnings which can actually create, I would call them small circles, which have the potential to become bigger circles. So if natural proximity is not delivering the desired sort of closeness or growth in economic ties, I think interdependencies have to be called in to create those opportunities which will set an example for this. I mean, sometimes I would say that, bilateral trade may be growing between different countries. But if you ultimately create a network of bilateral trade and bring them across a larger frame, you will have a regional trade. Richard, the building on this point of creating the supply chains, essentially, this is an example of supply chain. And Samir also referred to the fact that we have been focused on the ground and not the water. Do you see that investing where all the countries together can create projects which link the waterways in the Bay of Bengal area, the roadways. Also, perhaps India, Bangladesh can be the link to Southeast Asia. What are the kind of suggestions you have on developing new ideas which will enable trade and investment? I agree that if you look at the logistics cost in this region, it's one of the highest in the world. And because of inefficiencies, and you spoke about the inefficiencies, because of the way we are structured today. I mean, I'm giving a small thing. I heard in Nepal, they grow potatoes. It comes to India for washing and it goes back. I'm just giving a very small, very trivial example. But if somebody puts up a washery in Nepal, I mean, I'm just saying you can just wash it there only and do it. But taking that point away, even forget about linking with even India to link to India. If you use from Bengal, West Bengal into Northeast, Bangladesh is a route to go, waterways. So if there is more cooperation in this region, and I think this region, including India is never used or utilized waterways in a big way. And that actually brings down logistics costs very much. If you look at all the inland waterways Europe has created, that has brought it on considerably. And I think that is- Is this scope for public private investment and partnership on this? Yes, there is a big scope for it. And also the other point I want to put out here is there are nine highways being conceptualized in Asia, nine highways, out of which six run through South Asia, South Asia. So I think if these, somebody can take, say, okay, take some of these highways and create it.  So one left to see how to do it. And that's when this PPP thing will actually kick in and then say, how do you actually make it work? But PPP in the real sense, has to work in a model which is workable on all sides. And this will be more perhaps complex, but important because it may require other countries to- So one more example I like to give, I think, Samir, you raised the point on digital. I think let's not lose that, because the whole globe is moving towards digitization. Bangladesh has got one of the best internet telephony, this thing there. India's got very good software. India's got very strong on telecom. If both these come together, the internet is the way to go, where telephone is going to get, I mean, telecom is going to get onto the internet. I think if collaboration will come in all these areas, because like I said, each of these countries have their unique skills. Market sizes are different, but unique skills are there. If you can bring these skills, the IT powerhouse, the accounting powerhouse, the textiles, and we combine the waterways which you spoke about, if we combine it, we can create a huge market out into South East Asia, which we have ignored this part of the world. I think we need to move. And I think this South Asia can actually become the cooperation on this could be much better. Secondly also, we spoke about trade. I think global trade is almost dying. If your globalization is now taking a different tone, something new is going to emerge. What is that we don't know. But in my view, it's going to be more prosperous than what we have. There'll be some pain before that. There will be some pain, but there will be ultimate succession and it'll come from small trading blocks getting created. If I may add what he's saying about particularly trade in goods among our countries, one of the biggest problems is the non-tariff barriers. There's so many non-tariff measures. I think we all have to find some mechanism where we can remove these obstacles. At the same time, we have to work on mutual recognition agreements. We are standards among these countries. There should be like common standards for the region. Common standards. So that I think will create a lot more. It'll open a lot more. But that was my original question to you also, Minister. Who is going to build these common standards? Who's table does the document lie on? India being the biggest country, I think they have to take the lead. In fact, we have been discussing with India on this issue and we are getting some positive response. India has to lead the way. I want to jump in here on the word interdependency and I think the biggest interdependency hurtling towards us or that is emerging is around the whole issue of climate change and sustainable development. We keep talking about movement of goods and services. Are we talking about movement of people? I think we need to start belling the cat in many ways. When we talk about regional economic integration, there is an implicit element that allows movement of people as well. That's you look at the European Economic Community and other Asian ASEAN grouping. The African Union has launched Africa Passport. That's right. So I think one Indian proposition to the group which may create an attraction for a sub-regional grouping could be around visa regimes. So that's again a non-tariff barrier. But visa regimes is a big hindrance. There is a south visa which is for business. The second is, and I think this is extremely important, the largest chunk of our populations are still in that day of Bengal community engaged in fishing and the live of the oceans and the blue economy. I think that's again one new area where we must start working together on creating sustainable coastal infrastructure and ensuring that the fishermen and the coastal communities become partners and stakeholders in this effort to integrate. I think we have huge potential there. And the final point, I think, is that we must understand three sets of new rules for the 21st century are currently being written. First, the norms for the digital world, how you will conduct trade, how you will price data, how you will store it, how you will keep it safe, how you will encrypt it, et cetera, et cetera. Do we want to be passive recipients of what emerges from other parts of the world or should there now be a South Asian proposition on this is the way we should be managing data? And with 2.5 billion strong community, I think we should be taking the lead. That's one. Second new rules that are being written is around the whole development paradigm. Now, we have all signed on to a common UN deal last year in September. Are the South Asians talking about it? And the third and final point that we need to understand is that eventually Bay of Bengal community is going to be, the Indian Ocean is going to be witness to three or four big powers. So are we creating norms for the ocean? Norms that will allow safety and security of trade lines, trade links or sea links. And I think we need to start talking about the intersection of security with trade. And again, it boils down to the essential issue that framing of these ground rules and the structures, they have not happened yet. And perhaps that's why all the countries need to really rapidly come together under one roof, discuss one single framework, and say all the rules will be written under that. And I think that's the need of the other. Let me bring in some thoughts and questions from all our other participants here if you could introduce yourself and keep it short and brief so that we can take in lots of ideas. Sure. Can we have the mic? Let me collect a couple of thoughts and then come to one here and one here. Good morning. Yeah, go ahead, please. Good morning. I'm Kitna Hevake. I'm a global shaper from Colombo. One of the actors, an important actor in regional cooperation, integration in South Asia is ironically China, particularly with their one belt, one route framework. So I would like to know from particular from policy perspective as well as an investment perspective, how does this non-regional entities participation in regional activities influence that? And is a possibility of a BIMS-Tech trade agreement within a possible RCEP, the future of regional integration in South Asia? That's a lot of questions and we'll make a long answer, but good questions. So I think China does think of itself as South Asian also, but that's another story. Thank you very much. My name is Hamid Nuru and I'm with the World Food Program, Country Director in India. So I'm sure everybody expected to say, you know, where has food featured in this? You know, why am I here? Because this has to do with trade, but I will not therefore ask the question I wanted to ask. I'll do a one-on-one with the Cargill representative, Mr. Sarag. But just to make one or two comments from a general presentation, the first thing is there's a lot of lessons that need to be learned and I agree that, you know, looking at how we can revive blocks rather than looking at the whole is very important. Africa has gone through this and I am from Africa, Botswana. The regional economic communities like Sadiak, Ekoas, all the other, you know, this is exactly what they did and I think lessons can be learned from there. You don't have to reinvent the wheel on that. The comment on cricket I understood, but I say Africa, of course, is football rather than cricket. So where does food really come into this? This particular region now we have a lot more of these middle-income countries which are now, you know, springing up and really the role of food and food security is primary. Before you can even go into trade or health or education, you know, you have midday meals in schools, people go yesterday can get education. So this is really a primary thing considering that more than 50 percent of the hungriest in the world are within this region alone and yet this region is now is an economic powerhouse for the future. This is something that needs to really be addressed and I'll take it offline with those of you who I will speak with later on. Absolutely. I think food security is so critical for the region. One mic here please. My name is Minni van de Pol. I'm a partner with Baker and Mackenzie and I'm the Global Chair of Compliance and Investigations Group and one of the things that we haven't heard today is about risk. With every opportunity there is also risk and in this region one of the biggest issues that companies face is, you know, the risk of corruption, unfair competition and those types of compliance issues and unfortunately that crosses all the geographies that we have at the front of the room. So my question is are you going to also consider a common standard and approach whereby you will actually take these risks seriously and create an enforcement environment where companies understand what the rules of the game are because, you know, just like cricket this is a this is a common issue that that is shared. Thank you. So maybe what we'll do is that we'll probably end after this round of answers. I'll begin with Richard and come down the panel and request everybody to react to these issues. Richard, would you like to begin? So maybe I'll take the risk one. Yes, we didn't cover it because basically we were trying to see how to get the cooperation going and you know, even if you put something down on a paper you'll say yes, but we cannot do it because of this and but I think the risk issues are real and it's just not for the region. I think it's across the globe the risk issues. In fact, we had recently done a survey of the CEOs and the biggest risk that the CEO saw for India was a geopolitical risk as in the top three risks and cyber security is another one. The point which you talk about corruption is another area but just from an India perspective I can give you an answer and say that a lot of that is improved considerably. There has been strong moves in that direction so when the government gets serious and wants to move into that direction I think things can happen and we have seen it moving in a very positive way and there are a lot of global companies who operate in India who are able to manage in the system and not get, though you keep hearing stray cases here and there whenever they happen and recently we had one but I think this is being dealt with. I think the first thing we have to understand is any growing economy it's the pangs of a growing economy. All western economies when they grew and if you go back into the history I think it's replete with a similar kind of situations what they've also gone through so it's pangs of a growing economy prosperity not getting to everybody at the same level and that's why some of these things actually manifest themselves but as the prosperity grows I think this will slowly get more mature and it will get dealt with that's my personal view on this because I do a lot of work on this governance and other side and I can tell you it's improved considerably. Thank you so actually one of the very commonly used word in these discussions typically is the non-tariff barriers and a lot of that comprises of what you talked about and I think getting those barriers down is really about a lot of it is human element there. Do you want to also talk about food security even though he didn't ask you the question? He's been wise to stay off that because that can be a long discussion but yes I mean I think that's critical and you know and I've been thinking about it from a perspective of India setting this goal of doubling the farmer's income by 2022 and that obviously entails significantly improving productivity and we had this discussion yesterday under the same forum now if all this food was to be produced where will it go and so how do we place this growth in agriculture that we are looking for into the region and that would entail then bringing down the barriers. I think one of the point is very clear this is also the region with the highest incidence of poverty and food security. There have been good examples of how it has been addressed so sharing of best practices is one thing which is very easy to begin with. It's not just about food security it's also nutrition security which there are great examples in different countries that are being another thing which has come up and I think India's taken the lead in that which can be shared across the region is the whole concept of food safety which is quite closely linked to nutrition security so I think there is a lot of work to be done but to begin with I think the starting point has to be more clearer and closer information sharing. I think the awareness about what is needed where what can be produced where I think that common information needs to come on to a page and then better decision making can happen with the region as the perspective rather than local areas. Thank you. Minister Kamal also on the fact about is China part of South Asia yet or not? I see the question is the question is you are not taking it you know in the in a spirit we expected that you should take it that is a one belt policy so again I'm saying one belt was there in the past if you go back to the history then you'll see that that was there so everybody's trying to trying to come back or revisit the old things so that everybody can be benefited now after the demise of demise of Lehman brothers on 15 September 2008 after that what we have seen it is almost a decade in every first of the world most of the first of the world either there is the recession or there is deflation so and then a subdued scenario is still I mean first yeasts so in that on that basis we have to think we have to revisit our revisit our own position also we have to combine ourselves we have to integrate ourselves that is there is no denying to this fact so if we do that in that case we will have a lot of answers very easy answers or acceptable to everybody you see Benjamin Franklin in 1783 he made one observation the observation was that he was making he was saying I'm feeling sorry to say like that I've come up to this world little early I've not seen the discoveries I've not seen the wisdom I've not seen enough of education what will be coming next so it is true during he from now about 230 233 years back he was on to this all and during that time there was no economy during his time the size of the global economy only was 82 billion dollars buses now it is 78 thousand billion dollars imagine during his time he has no tap water he has neither any telephone nor any electricity nor any motorbike or motor or any motor car nothing like this so now we are better off compared to compared to that position and it does not take a long time again I'm saying you see right if you go back to the history you'll find in 1991 the parkivity income of the whole world was only one thousand dollars now it is eight times bigger it is eight thousand dollars and the forward level also about 100 years back it was 95 percent it was 90 percent plus was the over the level now it has come down to level of 12 percent so everywhere improvement is there what the world could not give us 200 000 years we got everything during the 50 years life expectancy has gone up more than double you know it was less than 33 years now it has gone 76 plus saying the pace of change is rapid and therefore South Asia can benefit so it is it is it is I'm I'm sure you'll have to take everything into proper perspective and then you will have the answers and you will see it is the time we'll have to integrate ourselves more intensely so that we can sustain our development we can keep up the pace of development and we can move forward together we should move forward together I'm saying again we should move forward together that is the only solution you know because South Asia I'm not South Asia by the year 2030 will be half of the world population will be living in this area and almost almost 30 percent of the middle-income people will be here and working-age population will be more than more than half of the total world you know so in that case this is a big region big area we'll have to think that way and we'll have to think big and we'll have to materialize those things correct for the many bit of our young for the many of our future generation and for the many bit of our people thank you mr. summer yes if I take the question of China first I don't think that any country in the world can afford to ignore China and in Sri Lanka we are certainly working very closely with China to improve our economy to develop our country but we are not doing that at the expense of any other country yes so that is the most important thing and we are we are well aware of the security but can our step and sarc or bimstack all work together do you see do you see possibilities there well I think most of the countries in the region for sure even Bangladesh included I think we'll need some to work with China to develop the country in some way or the other it doesn't mean that you can completely isolate them but it doesn't mean that you should also we must be aware of the risk you must aware of the security concerns that countries like India will have but once you address them I think there is a lot of positive development that can take place now for instance we are discussing a free trade agreement with with China so if we if we conclude we hope to do that by March next year manufacturers entrepreneurs can set up their plants the industries in Sri Lanka even from India and make use of that free trade agreement to export their goods to to China so there are so many advantages that you can you can have when you look take the issue of corruption in Sri Lanka we are taking that issue very seriously a new government has been placed for about over a year now and we have done a lot of we have made a lot of progress in that regard and we have minimized corruption I don't think it's possible to eliminate in total but there'll be some level of corruption but it's being controlled and as far as the government is concerned we are very open and transparent in all our dealings so we have addressed that very seriously and the third issue I think food security security is certainly a concern because the world is growing and in Sri Lanka we are self-sufficient in rice and because of the restriction of land now we have to look at ways and means of improving productivity in the other areas in agricultural products in particular so we have to use technology to see how we can improve productivity and be more efficient in producing goods thank you I'll take one minute from you sir you see we have discussed almost every firms only one point it has come to my mind you know because I should share with you the view statistic outlook in the economic arena it is we have talked about digitization we have talked about automation and all these things now this particular idea the way it is coming up I don't know how you will address this issue because already driverless taxes are in on the roads in Singapore agriculture in agriculture there will be no human being will be available all will be taken over by the machines so we will be producing the machines that particular machines will replace me that's coming up so you see that is another idea you'll have to think of right from now what Benjamin Franklin he could not see most of the discoveries I am also now apprehensive the discoveries what are coming up coming up in a big way and I think it's time to make plans how do you how do you adapt to the to those circumstances and I think that's one more important point on the agenda that South Asian countries have to talk to each other on which is so far not been on the agenda some of you probably have the last word good so on food security I think the point is right we have to move from obsession with volumes to nutrition and regional and sorry rural supply chains and infrastructure for better distribution I think that's no one is going to die because of volumes they will they are they are suffering because of lack of nutrition second on compliance and corruption I think I agree again with the panelists it's growing pangs if you want investment if you want global investors to be interested in in entering your geography you will have to start meeting best standards globally and it's it'll be useful if under any new arrangement that we come up we are propositional in putting forward those benchmarks and finally on on obor I think you we must recognize China is already in South Asia the question is how do you want China as an actor in South Asia no one is denying and no one is trying to say that we don't want Chinese investments or Chinese businesses and trade I think the question here is do we want to engage with them in a manner which is beneficial to all or do we want to be in an exploitative relationship what is clearly visible even in South Asian region I won't take the name of the country the country is aware of it is that curiously as their engagement with China rose they are again in in the midst of an IMF restructuring plan so it has been witnessed in many locations all over the world not only in South Asia that Chinese business and IMF restructuring go hand in hand so you start thinking about sovereign debts and is that the kind of relationship now if we work together as a region I think we can try to get the dragon to behave well and I think that is why as a proposition should be on how to manage that that new that new actor in this region on and like I said you know finally we are living in a world which has three generations living together the first will retire at 60 and will have to find meaning for 25 years of life they will require to be employed or gainfully occupied we are living we also have a second generation which is around my age who will never have the luxury of retiring we'll have to keep working to survive and finally we have the generation behind me who will never have formal employment as we know it and we have to find human value for all of them and that is why I was saying think about human value chains think about informality on the digital platforms think about you know activities that will make all these streaming millions that we have we are not a bane but in fact gainfully productive thank you so many and I think the only sentence I can use to sum it up is that we have to stop talking only bilaterally we have to start talking in a multilateral fashion and that will ensure that the multilateral interdependence is going to be far more beneficial than just bilateral dependence which could perhaps not always turn out to be what it is I'd like to thank all of you for being here and I'd like you to join me in thanking the panelists for sharing their views.


C-King for Ukraine. Germany to hand over multi-purpose helicopters to Kiev. Germany announced the allocation of six multi-purpose C-King helicopters to Ukraine states the German Minister of Defense Boris Pistorius. Pistorius participated in a virtual meeting of Rammstein where he announced that Germany would transfer six multi-role C-King helicopters to Ukraine. This assistance is provided in addition to the main directions specifically reinforcing Ukraine's air defense according to RBC Ukraine. It is a transport helicopter built by the Sikorsky Aero Engineering Corporation. The helicopter was developed under a contract signed on December 24, 1957 with the US Navy. The first flight of the experimental model took place on March 11, 1959. Serial production began in 1961. A total of 796 helicopters of all modifications were built and additionally over 600 helicopters were built under license. Ukraine had previously received such helicopters from Britain. It was reported earlier that on January 23, the 18th meeting of the Contact Group of Defense of Ukraine in the Rammstein format began. The head of the Pentagon Lloyd Austin urged the participants of the meeting to provide the armed forces of Ukraine with more life-saving ground-based air defense systems and interceptors. The Minister of Defense of Ukraine Rustem Umarov at today's meeting of the Contact Group on Defense of Ukraine in the Rammstein format discussed what the armed forces of Ukraine need to achieve a breakthrough. The head of the Press and Information Department of the Ministry of Defense of Ukraine Ilarian Pavliuk reported that within the framework of the regular meeting in the Rammstein format, issues of increasing supplies of long-range weapons to Ukraine were discussed.