Jeanne Loring: hES cell research, Bush, & her career

By Jeanne Loring

George Bush on human embryonic stem cells.
George Bush on human embryonic stem cells.

A stem cell anniversary: 18 years ago today that the US initiated funding of human embryonic stem cell research.

August 9, 2001 was a big day for me.  George W. Bush was the US president, and it was an understatement to say that I was not very fond of his policies; but that day he defined my career for the next 18 years.

That day Bush gave an 11-minute speech (see Youtube of the video below) at his Texas ranch that directed the NIH to start funding research on human embryonic stem cells (hESCs).

He made an awkward compromise that allowed federal funding for hESCs that already existed, but would not fund research on hESC lines made after that moment, 8:12 pm CDT.  Since all of those existing hESCs were made with private funds, it was a motley group that met in 2002 at the NIH to discuss how the funding would be distributed- among them were Jamie Thomson from Wisconsin, a handful of others from companies and institutions in the US, Sweden and Australia…and me.

I was at the NIH meeting because I had started a company several years earlier, and at the time of Bush’s speech, I had initiated derivation of cell lines from 9 human embryos using private investment.  My company, Arcos BioScience, was running on a shoestring because the Wisconsin Alumni Research Foundation (WARF) controlled Jamie Thomson’s 1998 patent that gave them ownership of all human embryonic stem cells, no matter who had made them. Their patent licensing fee was more than my company’s entire budget. To survive, a year later my company merged with another company (story in WSJ 2002), which later merged with another, and another; the much-merged company eventually took the name ViaCyte, and is currently conducting clinical trials for an hESC-based cell therapy for Type I diabetes.

We did get one of those first NIH grants for research on hESCs in 2002, and then in 2004 Phil Schwartz and I got a grant to run an NIH laboratory course on hESCs.  That grant supported my return to academia at the Burnham Institute in 2004. I was in the right place at the right time when CIRM (California Institute for Regenerative Medicine) began funding hESC research a couple of years later. Now 18 years have passed, the WARF patent expired in 2015, and my focus on pluripotent stem cells has taken me through professorships at Burnham and at the Scripps Research Institute to the company my colleagues and I started last year, Aspen Neuroscience, which plans a clinical trial for patient-specific iPSC-derived neuron replacement therapy for Parkinson’s disease.

Here are some words from Bush’s speech:

“Based on preliminary work that has been privately funded, scientists believe further research using stem cells offers great promise that could help improve the lives of those who suffer from many terrible diseases, from juvenile diabetes to Alzheimer’s, from Parkinson’s to spinal cord injuries. …research on embryonic stem cells offers the most promise because these cells have the potential to develop in all of the tissues in the body. Scientists further believe that rapid progress in this research will come only with federal funds. Federal dollars help attract the best and brightest scientists. They ensure new discoveries are widely shared at the largest number of research facilities, and that the research is directed toward the greatest public good.

I have given this issue a great deal of thought, prayer, and considerable reflection…

As we go forward, I hope we will always be guided by both intellect and heart, by both our capabilities and our conscience. I have made this decision with great care, and I pray it is the right one. Thank you for listening. Good night, and God bless America”.

I never thought I would say this, but besides the NIH and CIRM, I owe thanks to President Bush for supporting my journey along this path.

33 thoughts on “Jeanne Loring: hES cell research, Bush, & her career”

  1. Masha, I’ll give you one: Black slavery in America.
    Oh, here’s another one: Extermination of Jews in Nazi Germany.
    Let’s see, how about: Trial by fire in the Middle Ages.
    Oh, more recently: Tutsi genocide in Rwanda.
    These past atrocities of humans against humanity don’t continue now because once some said, “No more.”
    And I do believe that with continued education and protest of the problem, ignorance and self-interest will subside and give way to better treatment and care for even the youngest unborn human persons.
    For now, I will have to leave our discussion at this point of moral, ethical, social, and philosophical difference.
    Peace be with you.

    1. James, I fully agree with the top part of your comment.
      My best to you both. It’s healthy that we can have respectful dialogue even if we disagree on certain points.
      I don’t know of another place on the web where the kinds of stem cell-related issues we just discussed can be debated this way.

    2. I disagree with your interpretation of these examples as all of these atrocities were not stopped by the power wielding oppressors suddenly realizing their errors and throwing down their arms in moral revelation. They were stopped by even more powerful forces who gained the upper hand. Self-interest prevails as it is the most powerful evolutionary drive and the drive is our human nature.

      Thanks for the stimulating discussion and be well.

  2. Indeed, in human evolution, power over others is the manifestation of an evolutionary advantage, but whether that advantage is deemed selfish, aggressive, oppressive or barbarian, depends on your position in the struggle for resources. I cannot find a point in history where this drive has been “redressed successfully”. These highly evolved traits you speak of are a part of this drive and only highlighted to counter the argument that human beings cannot free themselves from their power quest, which is ultimately fed by the interaction of genes and environment.

    If we find a way to unanimously agree that a single-cell embryo from any source deserves to be treated as if it were a fully competent human being, with all human rights and as much liquid nitrogen as it needs, it will not be due to some mass epiphany but to some perceived or real advantage and a shuffling of the power positions. Altruism is a myth that we tell our children to release endorphins for our own selfish physiology.

  3. Masha, it’s not about souls. It’s about power and oppression for selfish motivations. Certainly, you are right that such human practices are common to our past and our present, and we will not be free of all them even in the deep future. But by your calculus many ills of aggression, oppression, and domination in the world that have been redressed successfully in the past would still plague the world. I’m not sure that we are evolution’s fittest, but we do appear to be the only evolutionary product that has the ability to reason about what is good and what is evil for our own species, as well as other creatures on the Planet. Not exercising such a highly evolved trait could be the sooner end of us; and certainly we benefit all when we individually seek to secure the greatest good for others despite our self-promoting tendencies. Civilization requires more energy and reason than barbarism. Save our embryos and fetuses, save ourselves. It’s that simple.

  4. Paul, your comment to Masha plays games with the meaning of “potential,” as genuinely and thoughtfully discussed by Masha. Masha refers to the specialized properties of human zygotic embryos, without experimental manipulation, to complete mature human development, currently if provided a gestational uterine environment. By your calculation, any cell, no matter what its origin or animal species for that matter, has the [potential] to be converted into a human embryo given that the required human ingenuity and engineering occurs to do it. But that fantastical insinuation does not equate any one of my or your mature, naturally limited potency, differentiated cells to a human zygote, no matter how that human zygote comes into being, even if by your fantastical suggestion. And I think you do recognize the incongruent, and even trivializing quality of your statement.

  5. James, all would subscribe to your reasoning regarding the treatment of human beings per se. But the point of divergence is the notion of when an embryo is regarded as such. Scientific, philosophical and, yes, ethical opinions are split between the moment of conception on the one hand, and a later time-point when the organism becomes sentient, or conscious, or shows signs of intelligence, or feels emotion, or pain, and so on, or for others, when it has a soul.

    With new technologies we are now asked not whether the single cell zygote has a soul, but whether the iPSC-generated single cell zygote made from adult skin has a soul. And there will be millions of them made solely for research. You asked if I want to live in a world in which such utilitarian pragmatist activities are promoted, and I say to you, we already do. There hasn´t been any other society on the planet since Homo sapiens became evolution´s fittest and the only way that your ideals would now prevail is by law, force or financial sweetners. C´est la vie.

  6. Masha, thank you for your address to A G’s statement. I will add though that if my argument were religious in basis, it would still be valid and of merit. Just like secular positions taken on this issue (e.g., utilitarian, pragmatic, ethical or moral), religious and theological positions are valid for making their case for how one group of human beings should treat another when the motivation is the opportunity for the first group to benefit from inflicting the demise of the second. Scientific arguments do not help us with these issues except, and importantly, to set our ideas for what is occurring in terms of human life and to set our expectations for what benefits might result from a given course of action, in this case human embryonic stem cell research. I have chided some of my fellow scientists for confusing, obfuscating, or outright lying about what is the current biological science understanding of the nature of human life at the earliest stage of human development, the zygote, or fertilized egg, or single-cell embryo. I have never been one to call this stage of human development a “potential” living human being, because by all of our scientific knowledge they/she/he already is. On scientific grounds, the youngest embryo is just as much as a living human being as a fetus, a new born infant, an adolescent, a mature adult, or an aged elder. This cellular developmental progression is the nature of mammalian life on Planet Earth (and in many cases plant life as well), including humanity. After first recognizing and acknowledging this scientific reality, thereafter we can have all sorts of arguments about how humanity should treat its youngest persons, but we should be clear that those young “balls of cells” are we just the same.

    Masha, a Japanese group just reported the production of mouse blastocysts (an early embryo stage) from iPSC cells. The artificial blastocysts did not develop well, but with time and more research, the problems encountered may be overcome. And yes, I am quite worried about the same group or other scientists will move on to parallel research to make human blastocysts, which are nascent living human beings. If this occurs, it will undo the original motivation for developing iPSCs, which I have viewed as a moral and ethical solution to allow research on pluripotency and the good things it might bring without the dilemma of having to kill nascent human beings as when producing hESCs.

  7. Following on from AG´s reply I can understand the impression that James´arguments appear to be grounded in a religious context, but they aren´t, they are, I think, derived from a purely humanitarian and moral standpoint. I believe James´protest (and I´m sure he will correct me if I´m wrong) is that these embryos are “potential or actual” humans, depending on your definition, and must be treated with the respect you would show toward any human being.

    But you also mention a key aspect of the issue that I was addressing too, are these “embryos” alive or not? I agree that they are not sentient beings, having no conscience or intelligence and not having the cellular architecture to create such processes. This is where James´armchair / pulpit sermonizing and the real world diverge, as his stance does not create any process or discussion likely solve the issue of the many embryos stored in cryo. Furthermore, regarding the the disparate opinion as to whether a ball of 10-100 undifferentiated cells is a human person, what is James going to say when we make sperm, eggs and blastocysts from iPSC cells (which he seems to accept as morally clean) – wouldn´t that make all cells potential humans?

    1. Masha, your point on IPSCs is a good one. IPSC technology would seem to possibly endow almost any human cell with reproductive potential. Are the skin cells on my arm or my blood cells, hair follicle cells, etc. a human being? Nope. Yet, someday they may be able to be used to make an actual new person via IPSCs. This illustrates that the “potential” to make a human being does not translate into equivalency.

  8. James,

    The points you’re making are clearly religiously based and have no basis in science. It seems that you take bits and pieces of logic and science knowledge and tailor them to fit your stance on ESC research. Scientifically and objectively, these “embryos” that were used for valuable research were not “alive” and as we all know, didn’t develop further onto the state of a living being. Your religious beliefs shouldn’t prevent the World’s progress in medicine and science. That’s the point of separation of church and state.

  9. Masha,
    We have no indication that they are suffering. However, as I have shared earlier, many families who do worry that they are decide to end the possibility of suffering by withdrawal of life support in a variety of honoring ways. The important moral and social issue here is that their deaths are not caused for the gain of others. This socially destructive impact of killing millions of nascent persons for research is what is lost on Jeanne, you, and others like you who adopt a utilitarian pragmatist view of the issue. “Willfully shouldering an ostensibly immoral decision [may] sometimes [be] the most ethically acceptable route,” but it is still an immoral route. The essential question is not whether you would choose the ability to contribute to the knowledge base of mankind over infinite suspended animation. Instead, it is whether you would agree to being killed, without your consent, to contribute to the knowledge base of mankind. And again, in the larger social context, do you want to live in a world in which such activities are promoted, even if in the purported name of human health benefits?

  10. Dear Masha:

    This is where utilitarians, who are so blinded by their view of human embryos as commodities to be donated, obtained, bought, and sold, cannot see the moral dilemma of ALLOWING NOTHING BUT PROCREATION for embryonic human beings who are now not selected for gestation to a mature life. We, us, society, all of us will never be made better by destroying these embryonic persons for any other purpose, even ones deemed to be a better alternative than leaving them in cryopreservation stasis until infinity if necessary. You don’t understand that the harm that is done to embryonic persons when they are utilized for the health benefit of others is not the only harm occurring. Equally significant is the harm that is done to us all when we must live in a society that doesn’t value the lives of weak defenseless human persons just because they are arbitrarily different than the more powerful. If you have lived in this world with the experience of unjust, immoral, social oppression, you may understand better why it is so important to some to limit trespasses against the lives of the weaker by the more powerful, which human embryonic stem cell research is a prime example of.

    1. Dear James, whatever ones personal moral convictions are, regarding the use or misuse of embryos, we have the reality of needing to decide what to do with them. I am surprised to learn that your regard the infinite imprisonment of these defenseless human persons as being better than ending their suffering. This is clearly an unethical stance in itself, albeit forced by the lack of a more ideal humane solution. I have lived in this world for 68 years and much of it in the USSR, DDR and Hungary. If you had experienced the unjust, immoral, social oppression that I have seen in real life, then maybe you could understand that willfully shouldering an ostensibly immoral decision is sometimes the most ethically acceptable route. As Jeanne Loring pointed out ESC research has been of immense value to medicine and the basic understanding of stem cell biology. I cannot speak for those unborn persons, but if I were faced with a choice of infinite suspended animation or the ability to contribute to the knowledge base of mankind, the choice would be very simple.

  11. The primary issue is not whether hESC is ethically acceptable, but what to do with the embryos left over from in vitro fertilization procedures? There are many more than can be used as planned or even donated (over a million in storage) and so their ultimate fate is either to be destroyed or to be used for medical training, or in a very few cases, to be used for basic or applied research. Now armchair bioethicists, what´s your take – burn them or create medicines?

    1. Jeanne F. Loring

      Hi Masha-
      It would be great if you could get an answer to your question- I’ve tried and failed.

      As I described in the original blog, I contacted several religious groups and philanthropists to suggest setting up perpetual liquid nitrogen tanks so that these embryos would not need to be destroyed. There were no takers.

      And just as an aside, human ES cells taught us how to culture human pluripotent stem cells. Yamanaka’s group could not have gone from mouse iPSCs to human iPSCs without knowing how different the human cells were and what their special culture conditions were. If grown like mouse PSCs, human PSCs die. Without hESCs, we’d have no human iPSCs – was not a theoretical issue- it was experimental science.

  12. Jeanne, the point you now make is not germane to the issue under discussion. The issue at hand is whether the “hESC experience” was obligatory for the development of human iPSCs. It was not. The basis for the grant of patents for hESCs has no bearing on the issue of the development of human iPSCs soon after the development of mouse iPSCs as I indicated earlier.

  13. Jeanne, your suggestion “that human iPSCs would not have been possible without human hESC experience,” could be either a rather poorly informed view or a very obtuse presentation of how scientific progress occurs. But it is certainly convenient for your proponent position for human ESC research. When Yamanaka’s group advanced their initial mouse cell studies to develop human iPSCs, of course they employed the then available culture media with proven ability to maintain the growth of human pluripotent stem cells, which were hESCs. However, if you are suggesting that, in the absence of such existing technology, no one would have figured out how to develop culture medium for deriving and maintaining human iPSCs, then you are denying decades of knowledge and expertise in mammalian cell culture science. Claiming “that human iPSCs would not have been possible without human hESC experience” is simply not tenable…on the merits. Why do you (and Steven earlier) need to go to this length to justify hESC research anyway? Let it stand on its own merits, which it has several; but also let it acknowledge its moral and ethical trespass as well, which I and others like me alarm is too harmful to justify the potential longer term benefits that have been promised. Paul, cut me off earlier, but I’m saying it again here. The well described epigenetic and genetic defects of hESCs and hiPSCs, the latter although without ethical concerns, are major ignored problems for their future medical success as promised now.

    1. Remember the WARF patent…composition of matter for all human embryonic stem cells? It was granted because the PTO agreed that no one skilled in the art would have figured out how to culture human ES cells.

      This is fun- I haven’t argued with anyone about that patent in years!

  14. Jeanne F. Loring

    Hi James-

    Have you ever cultured mouse ESCs and human ESCs side by side? They have different growth factor requirements and require completely different passaging methods. If you tried to treat human ESC or iPSCs like mouse ES or iPS cells, the human cells would die.

    My point is that human iPSCs would not have been possible without human hESC experience. All the methods are provided in our lab manual- Human Stem Cells, A laboratory guide. If you want to buy the 2nd edition, it’s available at Amazon.
    The third edition is in development.

  15. Dear Steven:

    The claim you make at the end of your brief personal history is often made by promoters of human embryonic stem cell research, but it is not a valid claim in the manner often professed, as you also do. Induced pluripotent stem cells were first made in mouse cells based on murine embryonic stem cell research, and no scientific findings from hESC research were required, or were even a factor, in their engineering and subsequent development. The valid manner for a claim of a role for hESCs in the development of iPSCs is given by Nobel laureate Shinya Tamanaka in his seminal 2006 Cell paper: “However, there are ethical difficulties regarding the use of human embryos, as well as the problem of tissue rejection following transplantation in patients. One way to circumvent these issues is the generation of pluripotent cells directly from the patients’ own cells.” The successful production of human iPSCs soon followed, but the only role that hESC research played was in providing the motivation for moral and ethical scientists to apply their ingenuity to addressing a moral and ethical problem in the scientific practice of their time.

    James Sherley

  16. Admin,

    That is quite disingenuous. Even ridiculous. In what regard? Let the other readers decide. Of course, you may convince yourself that this response also “violates” your rules. Truth can be offensive to some.

  17. Steven D. Sheridan

    I remember August 9th, 2001 vividly; Jeanne and I shared this crazy day. I came to work at Cythera (now Viacyte as Jeanne explains through several acquisitions including her own Arcos) like I assumed would be like any other day to make cellular models for kids and adults with terrible, and often end-stage, Type I diabetes to provide potential cures for an unmet need for pancreatic beta cells to transplant, to protesters with horrible signs of aborted fetuses, botched abortions, etc. blocking the entrance to the parking lot. When I got into the luckily well-guarded campus, remember gathering with other obviously shaken employees in a small conference room with shades drawn along with Jeanne and asked, “what happened?” Then realized that we had become very public in what we were doing and now the hESCs we developed to derive beta cells had become public knowledge and pronounced on the “Bush List”. We weren’t given a heads up, so were taken completely off guard.
    My immediate response was fear for my family, “Did they record my license plate number while coming in?” “are there news trucks at my house?”. I called my wife in fear to explain what had just happened and concerned about how our young daughter was getting home from school (I drove home to get her, leaving the company grounds past protestors after temporarily covering my license plates with tape). Even afterwards for days/ weeks kept vigil outside our home for fear of reporters/ protestors if they found out where I lived.
    Persecuting scientists is not a typical scientist experience, not since Galileo suggested the sun was the center of the solar system or Darwin suggested we evolved along with the apes. Though myself, and other developmental stem-cell biologists including Jeanne, felt that way that day.
    A great amount of pioneering work came from deriving protocols and studying human cell types derived from hESCs. Including the development of induced pluripotent stem cells (iPSCs) directly from patients, a new paradigm which would never have happened, were it not for the pioneers that derived and fully characterized hESCs.

  18. There are several Clinical trials in Australia with MSC for Graft vs Host disease. Graft-versus-host-disease (GvHD) is Cynata’s first target indication and a Phase I clinical trial has been completed using the lead Cymerus™product candidate, CYP-001. The RPE stem cells for dry AMD and Stargardt’s is moving along at Biotime . The field was set back by years with the purchase of OCATA by Astellas in 2015 . Very little to no progress has been report publicly by Robert Lanza’s group and the US has falling behind in the field.

    Jeanne Loring has been a very bright star in embryonic stem cell development . The key is working with MSC at the microenvironment tissue level with the CD4 /CD25 activation of the immune system . We need a good diagnostics test for the CD28 /CTLA-4 status at the tissue level and not blood…..The key cells will be Dendritic and MSC and NK Cells all from embryonic blastomere stage……Why? potency and migration to the site of need ……Adult cells do not migrate as well to repair and reboot and rescue injured tissue and that’s a good thing .

    1. Jean mentioned ViaCyte, which uses ESCs to derive insulin producing beta cells in an effort to treat type-I diabetes. They have been conducting clinical trials since 2014-15.

      I would not term this “ESC therapy” as that would be misleading, not to mention dangerous. This is cell therapy with cells reprogrammed from ESCs. That this is meaningful is a given.

        1. Indeed, for scientists familiar with the cell types, “ESC-based” makes sense. But non-scientists hearing about “stem cell therapies” may not be aware that “ESC-based” means that the therapeutic is a differentiated tissue (hopefully!).
          There is often confusion between adult stem cell-based / MSC / SVF therapies and ESC / iPSC-based therapies, which sometimes leads to the notion that MSCs will provide new tissues in different sites, because the literature reports ESC-derived beta cells or neurons, etc. A hierarchy flow chart might be a useful guide.

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