Thank you very much for coming, and thank you
very much for Easan and oap member, pr members to give a present to present my research
on my birthday. Actually, today is my birthday. Thank you. I would like to talk about my research,
“my life as a microchip”. Nowadays, there is no doubts
about the importance of drugs. When we get a fever, stomachache or some diseases, So we need to have drugs to cure those symptoms. And there is a huge market for the drugs now. However, for the pharmaceutical company They face a big problem to develop just one drug. Just one drug. For example, the time, over 10 years and the cost over 100 billion yen
to develop just one drug. More seriously, the third problem is failure at clinical trials or side effects for the patients. Those problems are quiet serious issues for all patients and their families and pharmaceutical companies. Of course there are a number of reasons.
But I would like to explain about it one by one. Here is one example. This compound. Do you know this compound?
Can you guess what is this? How about chemists? OK, this compound has a really long name
as showing here. But this compound has the other names like rofecoxib, or vioxx which is non-steroidal anti-inflammatory drug (NSAID) and one of the most famous drug in a world. I’d like to tell you about this story. Vioxx was originally commercialized by Merck For curing pain, osteoarthiritis and dysmenorrhea. So after getting into the market, there were a number of reports coming up to suggest that vioxx caused heart attack and stroke with long-term and high-dose usage. That’s a quite serious problem. After a long discussion, finally
Merck decided to recall this drug. Here is the stock chart on Merck in 2004, and as you can see, there is a big drop. And this is exactly when
Merck decided to recall this vioxx and lost 5 billion U.S. dollars immediately. Of course, there are numbers of reasons behind but I would like to point out one thing. The preclinical trials with such cute animals. Basically, preclinical trials were conducted to test drug safety, toxicity and other pharmacological tests. However, of course,
animal models are totaly different from people. As you may know. Maybe. There is a big gap behind. I hope. So, Even if we confirm that some drug are very safe with the animal model. But some drug might cause some serious toxicity in the patient. So by using animal models we can not predict
such a toxicity or side effects. Moreover, for the use of animal models
due to the ethical issues, we need to follow 3Rs, like replacement, reduction and refinement. Because we need to use large amounts of animals. But due to such a issue,
we need to try to follow such a 3Rs. On the other hand, instead of animal models we can also test drugs with biochemical and cell-based assay with micro-titer plates. as showing here. But, it’s quite obvious that this micro-titer plate condition are totally different from the condition in our body. The main difference is the circulatory system. Each tissue organs in a body are
connected through the circulatory system. And drugs also travel through the circulatory system and influence each organs differently. But by using micro-titer plates,
we can not test such an experiment. Moreover, for preclinical trials,
we also need to consider about ADME: absorption, distribution, metabolosim, and excretion. Those are very important parameters to test for drugs. However, using a micro-titer plate we can not test such a drug. we need have an alternative way to test such a ADME. So here, I would like to introduce our approach, Body on a Chip to mimic the human physiological condition with in a microchip. And actually, I have here.
This is a Body on a Chip. It’s a prototype. and I would like to introduce this one step by step. To develop the Body on a Chip, there are two key elements. One is iPS cells; the other is microfludiics. Moving forward to the iPS cells, induced pluripotent stem cells. iPS cells, we can obtain by using somatic cells to introduce a reprogramming factor. So these iPS cells have two distinct very important characteristics. The one is unlimited self-renewal. The second is differentiation capability into almost any kind of cell in the body. This mean that by using iPS cells we can obtain sufficient amount of tissue collection for further testing. Like drug screening. Moving forward to microfluidics. Microfluidics have advantages to control small size of liquid, like water, from nL scale. If you think about your body, actually, our body is consisted with 60% of water. and this water plays an important role. Like the circulatory system as I showed here again. Actually, as you can see here, you can realize that our body has a really complicated fluidic system. But by using microtiter plates, we cannot mimic such a fluidic system. So, microfluidics comes into play. We are microengineers, so we can establish micropipes, pumps, and valves into the microchip and establish a very complicated fluidic system as shown here. This is what my colleague established, a very complicated fluidic system, like a subway map in Tokyo Station. By using this one, we can make a circulatory system, or a go-through, or a stop-by. We can do many kinds of complicated stuff. So we have a capability to establish an artificial circulatory system in small devices, as I show here. Moreover, as I mentioned, we are micro-architects. So, we try to build a very comfortable house for cells. Actually, comfort is very important for the cell. If you think about your cell, if you live in a very uncomfortable house and cannot sleep well during the night, you cannot work during the day. That’s a problem. These things happen for the cell as well. Like a microtiter plate, we cannot get cells on function. Therefore, we need to build such a comfortable house for cells. Our approach to develop such a “Body on a Chip” is as follows. We prepare the microfluidic device which has the comfortable house for cells and circulatory system. Also, we prepare the microtissues from iPS cells as much as possible, then introduce into the microfluidic device. Then, we apply the circulatory flow with drugs to see what’s going on for the ADME. absorption, distribution, metabolism, and excretion. This phenomenon is totally different from other conventional techniques. This is our “Body on a Chip” approach. Because of the use of iPS cells, we can also establish personalized or disease-specific body on a chip. As you might know, some drugs affect each patient differently. It’s a kind of personalized difference. but the conventional method, we cannot test such a difference. However, if we can obtain the iPS cell from each person, we can also test the difference of those drug’s efficacy by using our “Body on a Chip” technology. So, this means that if we can create the iPS cells from all members of you, iCeMS, and if we can put it into a device, we can generate “iCeMS on a Chip.” This is one of my dreams. Thank you very much for your kind attention. But, I do have one more thing. So, I introduce “Body on a Chip.” But, is it only for people? Not really, right? If we can generate the iPS cells from animals, we can also generate “Body on a Chip” for animals. We try to explore more possibilities of the “Body on a Chip” for further testing. So we are aiming to secure endangered species. Nowadays, there are over 3000 endangered animals on earth. and there are facing the problem for their survival. Nowadays, the modern zoo are getting a very important role for the conservation of such endangered animals. But, if those animals got sick, they cannot cure those animals because they don’t have any effective medicine or drugs to cure those animals. One of the big reasons is that we don’t have any research tools to study about their diseases because it is so limited. Our approach to tackle this issue is as follows: if we can generate, or actually, we can obtain somatic cells from the endangered animal’s hair non-invasively. and then we can establish iPS cells out of that. Afterward, we can establish tissue collection from the iPS cells and then put them into the microfluidics to generate the gorilla, chimpanzee, and whatever we need for the “Body on a Chip” technology. So, as you may realize that we are aiming not only for the people we are also aiming for wild life conservation As a member on earth, I would like to contribute to the global health care of all animals living on earth. Thank you very much for your kind attention. [applause]