Stem cells, which can be transplanted into a human body and differentiating into multiple body tissues, have been perceived as fascinating words by many people. Just the announcements of related patents or theses draw interests and attention. At the same time, however, people still cast a suspicious glance to them because of scandals like the fabrication of theses by Dr. Hwang Woo-suk and controversies over bioethics.

One of the nation’s first-generation researchers into stem cell therapy is Professor Chung Hyung-min_정현민, director of Stem Cell Biology School of Medicine at Konkuk University Medical Graduate School. Professor Chung has about 60 stem cells registered in his name, more than half of the total this country possesses. He has also published more than 200 related papers. In the process, Chung had come to be labeled as an “authority on stem cells” even before anyone knew it.

Professor Chung kept alive embryonic stem cell research in Korea, which had all but been suspended since the Hwang Woo-suk scandal, by winning the government’s approval for somatic cell cloning embryonic stem cell research at Cha Medical Group in 2009.

In 2011, Professor Chung took the post of the CEO of CHA Medical Group’s CHA BIO & DIOSTECH (currently CHA Biotech), and also became the first in the world to succeed in inducing differentiation into blood platelet by using embryonic stem cells.

Professor Chung, who still strives to concentrate on stem cell research, says, "There are few people with much experience in the field of embryonic stem cell therapy research because it is so new." Korea Biomedical Review met with Chung to discuss the problems in the stem cell therapy markets and the direction in which researchers should proceed.

Professor Chung Hyung-min talks about improving systems, which is necessary for Korea to take the lead in stem cell research, during a recent interview with Korea Biomedical Review.

Question: You have experiences in research, business, and development of stem cell therapy.

Answer: I used to engage in fertility medicine related to in vitro fertilization, not as a doctor but as a scientist. That was back in 1998 when I was at Columbia University as a researcher. A new study of embryonic stem cell was on TV every day. Since I had handled sperm and embryo more than anyone else, I had the confidence I could do it. In January, I packed my bags, came back to Korea, and started research.

The experiences I had at the infertility center of Cha Medical Group were also very helpful. Babies were born when my skill was grafted onto obstetricians treating infertile patients. Even now, when I think about it, it still gives me the goose bumps. When I was working alone, all I did was research and putting my research results into my thesis. When I collaborated with doctors, however, I could treat patients. That was a rare experience for a scientist, which is why I wanted to continue research so that I can cure incurable diseases with stem cells. And I have been doing that research until now.

Q: The Ministry of Science and Future Planning has given you 10 billion won ($8.9 million) for stem cell research. How have you spent the money?

A: In 2015, the government selected us as the “Stem Cell-based New Drug Screening System Development Project.” We receive 2 billion won a year for five years. One of the most frequent failures in developing new drugs occurs when we conduct toxicity study in non-clinical trials. Even though a lot of research is needed, the data from animal tests have limits as there are differences from humans. Public opinion opposing it is also high to protect animals. Therefore, there are many needs for toxicity tests that do not use animals.

Using stem cells, you can make a heart, liver, blood vessel, skin, and other various parts of the body. The cells created are almost identical to those of the actual human body. This means far more sophisticated toxicology tests become possible. Furthermore, the new drug screening is possible as well. The effects can be measured immediately after the drug has been administered. We are conducting research on this. Besides, there are studies of cystitis. We are aiming to conduct phase 1 and 2 clinical trials under the approval of the Ministry of Food and Drug Safety next year.

Q: The stem cell therapy market remains stagnant even though it receives so many spotlights. What are reasons for this?

A: There may be a variety of reasons. There are only seven licensed items worldwide. There should be at least dozens of them to receive market’s assessment. For example, CARTISTEM is the only stem cell therapy in the world for treating cartilage damage. There need to be at least three to four competitors and more clinical results to make this happen. As of now, however, there are too few products.

Efficacy is also another reason. Some doctors are “early adopters.” To be used in clinical situations, however, there should be no alternative treatments to replace new drugs or the new drugs should be equal or superior to the existing therapies or drugs. When their efficacy is similar, the new drugs should have price competitiveness. The ease of procedure to use the product is also helpful. However, there has yet to be a medicine to meet these conditions. The same can be said of efficacy as well. Stem cell therapy is still a first-generation product in the market remaining at an initial stage. If I compare it to aspirin (created from willow trees), stem cell therapy remains at a point where we are just eating the willow trees crudely.

Therefore, the next step in embryonic stem cell research should be focusing on how to increase the effectiveness of stem cell therapies, how to simplify transplanting methods, and how to make mass production possible through standardizing them. The study of cell therapy products, stem cell treatments, and gene medicine started only 20 years ago. Given that it takes 10 years to develop a new drug, this means there are people with much experience in this field. It still is an area unfamiliar even to those who have first demand – doctors and hospitals.

Q: There are rising voices wanting an improvement in the system because of high production costs.

A: Stem cells are harder to operate on patients than other medicines because we have to inject cells. Also, because each treatment is patient-customized, the cost of it can’t help but be high. Due to the high production cost, it is not easy to recoup development costs. All this shows why we need to improve the system. Systemic improvement is under way vigorously worldwide as well.

In Europe, regulators classify stem cell therapy and gene treatment as advanced therapy medicinal products (ATMP), putting a priority on them in screening the applications for clinical trials and item permission. They give the benefit of preferential screening and preferential licensing to them. In Japan, too, officials give item permission to stem cell therapies if only they secure safety through phase 1 and 2 clinical trials, under the “Regenerative Medicine Safety Act.” We need to monitor Japan closely. Many companies are going to Japan because they can receive permits if they complete phase 1 and 2 trials.

Q: What will Japan get out of this?

A: Numerous hospitals in Japan can accumulate experiences concerning stem cell treatment. Regardless of whether the therapies are good or bad, they can build a base for stem cell treatment. Also, as more companies come to Japan, they create jobs. In particular, the stem cell treatment is an industry with strong ripple effects on related sectors. Demands are enormous for medical equipment, raw materials, and consumables. Japan has begun to localize these parts. Not only is Japan trying to develop regenerative medicine industry, but the country is also attempting to develop related industries as well.

Korea has introduced itself as a powerhouse in stem cell research. As things stand now, however, it may have to hand over the title to Japan. In the 1830s and ’40s, many people came to California for the gold rush. Like that, people are rushing over to Japan for the stem cell research and their market is thriving as well. That shows why improving the system is so important.

Q: Many experts point out that there are insufficient examiners in the Ministry of Food and Drug Safety (MFSD).

A: Examiners or inspectors at MFSD have far heavier workloads compared with their counterparts at the U.S. Food Drug Administration (FDA). Their expertise also lags behind because of rotating assignment. If the officials from the U.S. National Institutes of Health or FDA attend international workshops on stem cell therapies, foreigners flock to ask questions, and the U.S. officials give answers because they are best experts in their areas. In contrast, officials at MFSD are swamped with so heavy a workload. They need to improve the system and enhance expertise at the same time. I hope we will also redouble related workforce. MFSD is an agency responsible for managing the public’s right to health. There must be no loopholes within MFSD. I think it more than even the Ministry of National Defense.

Q: There are no stem cell treatments approved by the FDA.

A: The U.S. industry also expects the “21st Century Cures Act,” which passed the Congress early this year, will help to ease criteria for item permission. The FDA has been unfriendly toward cell therapies. The FDA's basic rule calls for drugs to prove how they are absorbed, metabolized, and discharged in the human body. However, stem cells or gene treatments have yet to prove these. The only thing that can be proved is how they are distributed. Thus, there has been no way for FDA to issue permission if it wants to. As of right now, no items have received final approvals, but some have entered into a later phase of clinical trials. I expect there will come some products approved by the FDA soon.

Q: There is a perception that the stem cells are safe.

A: Results from clinical trials conducted by various countries show few reports of adverse effects. So, we can predict the harmful effects of stem cell therapies are smaller, not bigger, than conventional treatments. Given that they are still at an experimental stage as medicinal products, however, we need to deal with illegal operation more sternly. Clinical trials conducted according to rules and under the regulatory framework have shown no major adverse effects yet. Accidents can occur, however, if we don’t follow proper procedure and administer them mendaciously

Many surgeries are using (uncultured) stem cells in the field of cosmetic surgery, including plastic surgery and dermatology, too. We need to legalize them within institutions, too. In Korea, if you divide and proliferate stem cells, it is classified as a medicine. But if you split the stem cell and use it immediately, it becomes a medical procedure. Currently, all they do in cosmetic surgery are medical procedures. They sit on the administrative borderline. People seem to use these procedures often as these are safe and easy. Therefore, there is nothing to hide. This must be made transparent. We need to make guidelines through relevant academic societies.

Q: As a first-generation researcher, what would you like to tell the next generation of researchers?

A: There are many scientists among my juniors and students, and all of them are working hard. The only regrettable thing is they change their minds too often. Our country’s research system heavily depends on the government. Depending on where the government's research funds move, researchers can’t help but follow them. Embryonic stem cell research was once a fad thanks to Dr. Hwang Woo-suk but was devastated in the wake of the forged thesis scandal. Afterward, a lot of attention went to adult stem cells, which also drew lots of researchers. More recently, with the introduction of induced Pluripotent Stem Cell (iPS), researchers of adult stem cells quickly shifted to iPS. They also rush to convergence technology, such as bioprinting and Organoid.

If this continues, then scholars will lose their identity. Once academics set their sight on a particular field, such as embryonic stem cells, adult stem cells, or ES stem cells, they must follow it to the end. The government should not concentrate funds on a specific field of research just because it is hot. If researchers give up their existing research to shift to emerging trends, they become fast followers at best. They can never be frontiers.

hwz@docdocdoc.co.kr

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