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The East African : Jan 21st 2017
JANUARY 21-27,2017 Q&A WITH: SHINYA YAMANAKA The stem-cell revolution is on the horizon and with it new ethical issues He shared the 2012 Nobel Prize in Physiology or Medicine for reprogramming mature cells into iPS cells. But progress on new treatments has been slowing. He spoke to NYT’s WALLACE RAVVEN In 2001, US President George W. Bush issued an executive order banning federal funding for new sources of stem cells developed from pre-implantation human embryos. The action stalled research and discouraged scientists. Five years later, a Kyoto University scientist, Shinya Yamanaka, and his graduate student, Kazutoshi Takahashi, reenergised the field by devising a technique to “reprogramme” any adult cell, such as a skin cell, and coax it back to its earliest “pluripotent” stage. From there it can become any type of cell, from a heart muscle cell to a neuron. The breakthrough sidestepped the embryo controversy, offering researchers an unlimited supply of stem cells. There has been great enthusiasm and confidence for nearly 20 years that the use of stem cells will lead to powerful new treatments for a range of diseases. Now, 10 years after your discovery, what treatments have been developed? We are still in the early stages. In 2014, Masayo Takahashi and her colleagues at the Riken Centre for Developmental Biology had great success using iPS cells to treat macular degeneration. They took skin cells from a 70-year-old patient and derived iPS cells from them. They then differentiated the stem cells (directed them “back down” the normal developmental path) to become adult retinal cells. These were transplanted into the patient’s eye to treat the disease. That was a huge success. She sees much better now. Have more patients been treated? Before the transplantation for the second patient, we checked the genome sequence of the patient’s iPS cells and we identified a mutation in the cells. So we did not proceed. The pluripotent stem cells have the ability to proliferate rapidly and infinitely. But it’s a double-edged sword. After multiple cell cycles, the chances of mutations increase. This could include mutation to produce an oncogene that can cause cancer. So these treatments are now on hold? Yes. We are developing allogenic stem cell lines — stem cells from donors. They would not be the patient’s own, but compatible cells to transplant into the patient, much like blood transfusions with compatible blood types. We are performing rigorous quality tests, including sequencing the stem cells’ genomes to be sure the cells are free from cancer-causing mutations. We perform tests on adult retinal cells generated from these stem cells to ensure that they function as normal retinal cells, and those cells are transplanted into mice or rats for a year to assure they are safe. That’s very different from the way stem cell treatments were originally described to the public. It was going to be “personalised” medicine — using the patient’s own stem cells to generate the adult cells without risk of rejection. Well, we realised that it would take a great deal of time and would be unrealistically expensive to carry out the deep sequencing and animal studies for each patient’s cells. How many compatible donor cell lines do you expect will be needed to cover the Japanese population? Not that many. One particular line — just one — can work for 17 per cent of the Japanese population. We estimate that, altogether, about 100 lines will suffice for the 100 million people in Japan. How many lines would be needed for the more diverse US population? We would need only about 200 lines. Was the promise of stem cells overstated? In some ways, yes, it was overstated. For example, target diseases for cell therapy are limited. There are about 10: Parkinson’s, retinal and corneal diseases, heart and liver failure, diabetes and only a few more — spinal cord injury, joint disorders and some blood disorders. But maybe that’s all. The number of human diseases is enormous. I don’t know how many. We can help just a small proportion of patients by stem cell therapy. Why so few? We have more than 200 types of cells in our body. But the diseases I described are caused by loss of function of just one type of cell. Parkinson’s disease is caused by failure of very specialised brain cells that produce dopamine. Heart failure is caused by loss of function of cardiac heart cell. So, that’s the key. We can make that one type of cell from stem cells in a large amount, and by transplanting those cells, we should be able to rescue the patient. But many other diseases are caused by multiple types of cell failures, and we cannot treat them with stem cell therapy. What are your biggest concerns about the future of stem cell treatments? I think the science has moved too far ahead of talk of ethical issues. When we succeeded in making iPS cells, we thought, wow, we can now overcome ethical issues of using embryos to make stem cell lines. But soon after, we realised we are facing new ethical issues. We can make a human kidney or human pancreas in pigs if human iPS cells are injected into the embryo. But how much can we do those things? It is very controversial. These treatments may help thousands of people. So getting an ethical consensus is extremely important. The EastAfrican OUTLOOK 23 Uganda launches menengitis vaccination The govt seeks to achieve 80 per cent vaccination coverage of the 1-29 targeted age group in high risk areas. Pic: File By EVELYN LIRRI Special Correspondent UGANDA HAS launched a mass vaccination campaign against Meningococcal meningitis in selected districts that lie within the meningitis belt of sub-Saharan Africa. The five-day campaign began on January 19 and will continue until January 24, according to the Ministry of Health. Meningococcal meningitis is a bac- terial form of meningitis, which covers the brain membrane and spinal cord, and can cause damage to the brain in 50 per cent of cases if not treated on time. In December 2016, about 20 cases of BIO Background: Shinya Yamanaka was born in Higashiosaka, Japan. He studied for his medical degree at Kobe University and later earned his PhD from Osaka City University in 1993. After spending several years at the Gladstone Institute at the University of California, San Francisco, he returned to Osaka, but later moved to the Nara Institute of Science and Technology, where he began his Nobel Prize-awarded research. Shinya Yamanaka has been affiliated with Kyoto University since 2004. Experience: Yamanaka directs Kyoto University’s Centre for iPS Cell Research and Application. He also leads a small research lab at the Gladstone Institutes, affiliated with the University of California, San Francisco, where his group studies the molecular mechanisms that underlie pluripotency and the factors that induce reprogramming. the disease were reported in the central region of the country in the district of Nakaseke. Health officials say the outbreak has been contained, but the threat persists. The meningitis bacteria are trans- mitted from person to person through droplets of respiratory or throat secretions. Common symptoms of the disease are fever, headache, stiff neck, back pain and changes in the mental status of the affected individual. Health Minister Jane Ruth Aceng said the mass immunisation campaign will run in 39 districts, mostly in the north, West Nile and western regions of the country. “The objective of the campaign is to immunise the population belonging to the 1-29 age group and achieve at least 80 per cent vaccination coverage in the high risk regions,” said Dr Aceng. Although the disease can affect people of any age, Dr Aceng said the risk is often higher among infants and young children. Uganda lies within the African meningitis belt, which stretches from West Africa to the eastern region of the continent. Several outbreaks have occurred in the country in the past, especially in the in the West Nile and northeastern regions. Health experts say meningitis thrives mostly in hot and dry environments that are overcrowded. “The dust and cold nights that char- acterise the December to June period increase the risk of disease transmission,” said Dr Aceng. She added that people living in overcrowded houses and large population displacements further facilitate transmission of the disease.
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