Fake Science News? Yamanaka’s iPS Stem Cell Admissions -- and the Other Elephants in the Room

Dianne N. Irving
copyright January 29, 2017
Reproduced with Permission

I. Introduction

A great deal is surfacing these days about highly questionable research that involves the use of iPS cells ("induced pluripotent stem cells"). See, e.g., " In vitro gametogenesis: Bordering science fiction" , at: http://www.genethique.org/en/vitro-gametogenesis-bordering-science-fiction-66917.html#.WIZJjr1bHag . (See also Irving, "What you need to know about ‘IVG’ (in vitro generated gametes)" , (March 20, 2014), at: http://www.lifeissues.net/writers/irv/irv_221invitrogeneratedgamete.html . Another example is "Human-pig embryos created by scientists in breakthrough for organ transplants" , (January 26, 2017), at: http://www.telegraph.co.uk/science/2017/01/26/human-pig-hybrids-created-scientists-breakthrough-organ-transplants/ .

Yet the reliability of the science involved, and even the possibility of much real success of such scientific research using iPS cells in patients in the future was surprisingly awkward and timidly addressed by Yamanaka in a recent New York Times interview: "The Stem-Cell Revolution Is Coming - Slowly: A Conversation With Yamanaka" , (January 16, 2017), at: https://www.nytimes.com/2017/01/16/science/shinya-yamanaka-stem-cells.html?_r=2 . FYI the full article is copied below at the end.

II. More Elephants in the Room

But while Yamanaka admittedly points to some very important "elephants in the room" concerning iPS research, I’d just like to briefly note a few other "elephants" that are also involved in such iPS research that need much more extensive discussion. The issues concerning iPS research are not just "ethical" issues, but "scientific" ones as well. They are intertwined.

Elephant #1: Ethical Research Must Use Accurate Science

According to the international Nuremberg Code of Ethics , the first ethical requirement of scientific research is that the science used is accurate , as it is the starting point for determining what research is ethical or not. As the old wisdom warned, "A small error in the beginning leads to a multitude of errors in the end"! The Nuremberg Code also requires that the researchers performing the research are academically qualified and experienced in the field the research they are performing is in. (See Irving, "Current Epidemic of Scientific Fraud and the Nuremberg Code" (November 12, 2016), at: http://www.lifeissues.net/writers/irv/irv_235currentscientificfraud.html ).

However, it is well known that much of the "science" claimed especially by the "genetic engineers" involved is erroneous or non-existent, and most of these researchers do not have the proper and relevant Ph.D’s in genetics required to perform such genetics research. (See Irving, "References: CRISPR Gene ‘Editing’, ‘The’ Human Genome Project, Personalized Medicine’, 23&Me -- and Genetic Junk" (November 30, 2015), at: http://www.lifeissues.net/writers/irv/irv_230references.html ). Is that "ethical"?

Elephant #2: "Foreign DNA" of Vectors Used Cause Immune Rejection Responses in Patients

Scientifically, it is also well known that in order to produce iPS cells it is necessary to use "foreign" DNA from various bacteria and viruses (called "vectors") in order to both "deprogram" the original adult cell as well as to then "reprogram" the so-called "pluripotent cells" to the desired more mature cell, tissue or organism. Even aside from genetic mutations in the iPS cells due to the extensive manipulation of the cells involved, such "foreign" DNA of the "vectors" will be seen as "non-self" by any patient into whom such reprogrammed cells, tissues or organs are inserted -- thus triggering the patient’s immune system to reject them . And this would be true even if the patient’s own mature cells were originally used. Indeed, human patients’ immune systems are so sensitive that they can even detect very minute differences in just one atom in a huge molecule that has been injected into them. In fact, many patients have died from such immune rejection reactions. Is that "ethical"?

Elephant #3: Some "pluripotent" stem cells are really "totipotent"

Scientifically, it is also well known that many of the so-called "pluripotent cells" are actually "totipotent" cells -- and thus capable of being "regulated" back to a new whole human embryo if regulation is successful. Even Gurdon admitted this during one of his many conference presentations at the Vatican (see "Top researcher: iPS cells ‘probably’ already embryos, have already made cloned animals" , at: http://www.lifesitenews.com/news/top-researcher-ips-cells-probably-already-embryos-have-already-made-cloned ). In fact, this is precisely how naturally occurring human monozygotic twins are asexually reproduced in vivo within the woman’s body, as well as the kind of cloning technique used in vitro for decades in IVF and ART "infertility clinics" to asexually reproduce more embryos for implanting into infertile women. BTW, they also use the "twinning" technique in IVF and ART research laboratories as a source of new living human embryos to use in their destructive experimental research. Is that "ethical"?

Elephant #4: The Source of the Original Adult Cell is Relevant

Scientifically, many iPS research is performed using cells from male human fetus foreskin (oddly such cells were categorized as "adult stem cells" early on!), and it is already documented that one of the reasons why research labs and companies buy human baby body parts from Planned Parenthood is to use those baby body parts to produce stem cells. (See Irving, "Planned Parenthood and Human Fetal Body Parts: Sections of Main Legal Document (1993 NIH Revitalization Act)" , (July 16, 2015), at: http://www.lifeissues.net/writers/irv/irv_228humanfetalbodyparts.html ; also, "Planned Parenthood's Website ‘Glossary’ - Fake Science, Phobias, and Sexually Obsessive Definitions" (June 26, 2016), at: http://www.lifeissues.net/writers/irv/irv_233plannedparenthoodglossary.html). Is that ethical?

III. A Whole Herd of Elephants in the iPS Research Room?

In fact, I could continue with such examples re iPS cell research, probably indicating a whole HERD of elephants in the room. Imagine if even just the money and funding that has been absorbed in iPS research could have instead been provided to good properly credentialed researchers to help successfully cure many diseases instead. But hopefully at least some of the intertwined scientific/ethical issues involving iPS research will be taken more seriously now and widely publically discussed in the near future. Indeed, most importantly, innocent vulnerable human lives depend on it -- both those who take part in iPS clinical trials and those who will bear the brunt of damaging products derived from them.

For more "elephants" and documentation -- both scientific and ethical -- see also Irving :


The New York Times
January 16, 2017
by Wallace Ravven

The Stem-Cell Revolution Is Coming - Slowly

A Conversation With Yamanaka

Shinya Yamanaka directs Kyoto University’s Center for iPS Cell Research and Application, and leads a small research lab at the Gladstone Institutes, which is affiliated with the University of California, San Francisco.

In 2001, President George W. Bush issued an executive order banning federal funding for new sources of stem cells developed from preimplantation human embryos . The action stalled research and discouraged scientists.

Five years later, a Kyoto University scientist, Shinya Yamanaka, and his graduate student, Kazutoshi Takahashi, re-energized the field by devising a technique to "reprogram" 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. Dr. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for reprogramming mature cells into what are now called induced pluripotent stem cells, or iPS cells. Still, the march toward new treatments has been halting .

Dr. Yamanaka directs Kyoto University’s Center 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 .

I interviewed him recently in San Francisco. Our conversation has been edited for length and clarity.

[Q.] 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?

[A.] We are still in the early stages . In 2014, Dr. Masayo Takahashi and her colleagues at the Riken Center 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 brighter now.

Have more patients been treated since then?

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 increases. 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 assure 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 "personalized" medicine - using the patient’s own stem cells to generate the adult cells without risk of rejection. Well, we realized 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 percent 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 United States population?

We would need only about 200 lines .

Was the promise of stem cells overstated?

In some ways, yes, it is 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 portion 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 specialized 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 the prospects for the other nine or so diseases that you say stem cell treatments can address?

I think it’s likely that clinical trials will be well underway for many of these diseases in the next decade.

Your discovery has not entirely replaced embryonic stem cells for potential treatments. Different applications work better under different conditions.

How important is the new strategy to reprogram adult cells back, but not all the way back to stem-cell stage - more to a state that is still somehow specific to the organ the cells came from?

That is called direct cellular reprogramming, and it might work better than iPSC if, say, we need to replace all the cartilage in an elderly person’s knee. But iPS would probably be the choice if we are treating a younger person who only has a small lesion in the knee. We could make good cartilage from iPSCs and transplant that purified cartilage to that small lesion.

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 realized we are making 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 .

What is needed before patients can receive stem cell treatments for the 10 or so diseases you identified?

Time and money.

You know, my father had a small factory. He injured his leg in the factory when I was in junior high. He had a transfusion, and he got hepatitis C. He passed away in 1989.

Twenty-five years later, just two years ago, scientists developed a very effective cure. We now have a tablet. Three months and the virus is gone - it’s amazing. But it took 25 years. iPS cells are only 10 years old. The research takes time. That’s what everybody needs to understand.