This comment today from a reader, responding to Miracles may be Meaningless:  

“Conquering that embryonic cancer cell has proved impossible to overcome during the decade since Thomson’s initial discovery and no one is even claiming serious progress.”

Huh…? Geron is expected to go into the clinic with the hESC GRNOPC1 cells this quarter. Also, at the FDA’s invitation, they will present the IND “bar” for future biologic INDs next week. 

Their recent 30,000 page IND submittal documents the results of over 2500 rat studies with complete spinal cord lesions given injections of these cells. They document completely controlling teratomas via differentiated cell maturity / purity, thereby eliminating cancer and teratomas through GMP purity specs. 

I could go on but, obviously, perhaps this gentleman should stay tuned next week when the future becomes more contemporary.

Ref: http://www.Geron.com

Editor’s note: I received this comment yesterday, which I’ve posted in full below. In the interests of disclosure, the author is the founder of an adult stem cell company, VesCell. The company is sponsoring several clinical trials, which can be found at ClinicalTrials.gov

¤ ¤ ¤ ¤ ¤ ¤ ¤ ¤ ¤ ¤ ¤

Jamie Thomson, the father of embryonic research since he isolated the first line of embryonic stem cells in 1998, recently discovered, along with a Japanese associate, a method of creating faux-embryonic stem cells from adult skin cells, as announced in November 2007.

Virtually all of the stem cell writers in America declared the stem cell wars were over. “We can make embryonic stem cells from skin, so there are no moral issues!” they exclaimed. As is normal for embryonic publicists, they were years premature. We are no closer to real cures for real humans than we were before the new miracle. Embryonic cures cannot sail, this decade or next.

On the day after the big press release, I wrote that the Thomson announcement was a non-event; only that the embryonic movement needed its “miracle press release of the month,” and Thomson gave them one, inadvertently I am sure, since Thomson has never been anything but an honest man of science. His level-headed statement on the so-called miracle is refreshing when compared to the cheerleaders: “I believe these new results, while they do not eliminate that controversy, is probably the beginning of the end of that controversy,” Thompson said. ”Even though we have this nice new source of cells, it doesn’t solve all the downstream problems of getting them into the body in useful form.” Now you know why I respect the good doctor as much as I do. Few other embryonic researchers could make that underlined statement and expect to keep his job; but Thomson is untouchable!

You see, I look at embryonic stem cells from one perspective only: “Does this advance in knowledge bring the treatment of incurable diseases by implanting embryonic stem cells into suffering humans one step closer to mankind.” In this case, the answer is a resounding “NO!

Let us take a look from the real world of science rather than the science fiction world of the embryonic cheerleaders. The majority of these cheerleaders in America do not know that embryonic cells come from cancer cells and those cancer cells come along with embryonic stem cells in every lab in the world; witnessed by the tumor growth generated among the animal subjects in the animal trials….. a major obstacle that must be overcome before an ESC can be implanted into a human being. The reason they don’t know it is that the word “cancer” has been prohibited from being mentioned in association with “embryonic” in virtually every newspaper and medical journal in the land.

But the movement’s censors could not keep the word “cancer” out of the Thomson 2007 promotion, since Thomson put it in himself, as did his colleague Dr.Yamanaka and other quoted serious researchers. The same thing happened in 2006 when an honest embryonic researcher at the University of Rochester, after his team virtually cured his lab animals of Parkinson’s, was forced to watch as those doomed animals all developed tumors. “Cancer” appeared in the reporting medical journal and the spin doctors were forced to use it in the newspapers. The researcher was brutally honest about the events, which is why the Washington Post refused to print his most damning quotes and why the censors are still doing their best to keep “cancer” and “embryonic” from appearing in the same newspaper articles. You won’t find it in USA medical journals either, unless the reported event screams it out, as it did in Rochester.

That, and Thomson’s efforts to keep the truth in view (not an easy task in America, even for him) was the clue that convinced me this whole “miracle” was virtually meaningless as to the only thing that matters: “Where are the embryonic cures for human beings, or even animals, for that matter?” The answer is “further away than they seemed to be in before the announcement—and that was real far away.” Over the intervening weeks, serious embryonic people started to realize the truth. Please note I am not saying the latest breakthrough isn’t important, only that it does not bring embryonic implants into humans any closer.

Why?

FIRST, Thomson and friends must confirm their findings, meaning that some other research group must duplicate them elsewhere; and the consensus seems to be a year or two. Merely SOP in science, no argument there.

SECOND, researchers must conquer the cancer issue if they even dream of the FDA considering an embryonic stem cell trial. Conquering that embryonic cancer cell has proved impossible to overcome during the decade since Thomson’s initial discovery and no one is even claiming serious progress. They like to blame their failings on Bush, but this ignores thousands of researchers working around-the-clock around the world, mostly in countries with government funding and NO government restrictions. The manipulations of the pro-embryonic media prove how desperate they are to keep that information from their readers, the majority of whom are “true-believers.” Their readers, overwhelming pro-embryonic, have no idea that cancer is even a problem, let alone that nobody, not even Thomson with his latest triumph, has yet come up with a way to avoid it.

THIRD, they must conquer the rejection problem, a problem “solved” by transplant cardiologists who have no choice but to permanently compromise the dying heart patient’s immune system to prevent rejection of the new healthy heart. Permanently compromising the patient’s immune system is NOT an option for embryonic researchers.

FOURTH. The availability of embryos for research, Bush or no Bush, is a problem. Without a doubt, the cost of research embryos adds to the already super-high cost of embryonic research. For a complete report on this issue from the Rand thinktank, click here.

FIFTH, and this will come as a shock to those who closely follow the movement, is that the only bragging point of embryonics is that their cells are “pluripotent,” which means they can presumably become any cell in the human body, and therefore help any part of the body get better. Some are beginning to realize what I said in 2006: “Pluripotentcy is a two edged-sword.”

The best researchers in the world, on five continents, all know that science cannot begin to control the embryonic stem cell’s ability and desire to become whatever it darn well pleases. Good embryonic researchers can train their cells to significantly help patients with many different diseases, but once the cells are finished doing that, off they go, wherever and whenever and however they wish and that “however” too often results in tumors. In two words, as of the beginning of 2008, embryonic stem cells are unstable and unpredictable. The Curse of the Pluripotent! But read on: it gets worse.

Too many snippets are coming out of the real world of science to allow such an easy path to human treatment. The strange thing is that the leading embryonic scientists in America, but not the media giants, are actually pulling in their horns after the Thomson announcement!

First thing I noticed was the fear of the “reprogramming” that Dr. Yamanaka used to revert the skin cells all the way back to embryonic cells. Embryonic stem cells are already unpredictable, and Yamanaka’s method figures to raise the level of unpredictability. That makes them impossible to use on humans. That is not Don Margolis talking; this is from Dr. George Q. Daley, a stem cell researcher at Children’s Hospital Boston, who concludes:

“But for the ultimate goal of getting cells into a patient, it’s a lot less clear. These cells may never be useful for direct therapy.” Amen, Dr. Daley! For a guy who earns his living in embryonics, your honesty is refreshing!

Across town there is another embryonic research leader who is even more adamant than Dr. Daley. From Boston.com:

In what is even more of a lurking threat, the process uses retroviruses to carry the genes into cells. These viruses can disrupt the normal function of DNA and also can spur the birth of cancer cells.

Some proponents of reprogramming argue that problems from genetic modification and use of viruses are purely technical and easily surmountable. But other stem cell researchers are skeptical that reprogrammed cells or specialized cells produced from them will ever win approval for use in humans. “It will never be approved [by the FDA] to put these cells in a patient,” said biologist Douglas A. Melton, co director of the Harvard Stem Cell Institute. “The retrovirus can be a Trojan horse that can carry all sorts of problems.” (Thanks to Boston.com)

What is astonishing about these quotes is that they both come from Boston, the hotbed of embryonic exaggeration and adult stem cell denigration. FYI, there is no bigger embryonic research center in the world than Harvard, and the only difference of opinion between Co-Director Melton and myself is that he believes that real embryonic cells can, someday soon, safely be put into a human being, and I do not. I repeat, only an opinion, on both our parts.

Don Margolis

by Christopher Scott

In the New Scientist, I posed this question: should parents pay to have their child’s cord blood stored or instead donate it to a public cord blood bank?

My answer:

“If the couple already has a child with a life-threatening blood cancer, then banking the cord blood of a healthy newborn sibling is a fine idea, because that blood could save the older child’s life.”

Blood cancers are rare. In fact, a child has only between one in 1,000 and one in 200,000 chance of needing an infusion of his or her own cord blood later in life. The bigger promise advertised by some private banks pivots on the supposed power of cord blood to cure common illnesses such as diabetes, heart disease and Alzheimer’s. Some advertisements claim future cures for all of these, and may even be used to grow new body parts.

But wait a minute:

“Cord stem cells are scarce, and therefore not useful for most adults, who need large numbers of cells for transplants. Some assert that cord stem cells are powerful because they ignore their bloodline heritage and change into a multiplicity of cell types, including heart muscle and brain tissue. But this is hotly contested, and researchers are slugging it out experimentally, testing whether cord stem cells are as potent as the more optimistic scientists and cord blood banking companies claim.”

I argued that some claims about the therapeutic potential of cord blood were overstated, and that it was wrong to advertise that cures or treatments for complex diseases using cord blood were right around the corner.

Two weeks ago, the American Medical Association (AMA) issued ethical guidelines for how physicians should talk to parents about donating their babies’ umbilical cord blood. The vote was clear: mothers should be encouraged to give the blood to public cord blood banks. The guidelines also suggest that doctors obtain the consent to donate before the mother goes into labor, disclose any ties they have to a cord blood bank, and not accept fees for a cord bank referral. In January, the Academy of Pediatrics said parents should consider private storage only if an older sibling has cancer or certain genetic diseases that can be successfully treated with cord blood.

Cord stem cells are powerful: I’ll explain in future posts what science says about the cells, and how research is trying to sort out how these cells can treat disease.

During the holiday season, the spirit of giving in hosptials should take another form. Parents can donate blood to public banks. That would increase the likelihood that a desperately sick child or adult would benefit.

Illustration courtesy of the New Scientist

Zach Hall is former president of the California Institute for Regenerative Medicine. Susan Solomon is CEO of the New York Stem Cell Foundation. A version of this essay appeared 30 November in the Huffington Post. Find TSC opinion and information on the recent stem cell discoveries here, here, and here.

¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤

By Susan Solomon and Zach Hall, Ph.D.

Nothing would give the millions of people afflicted with heart disease, diabetes, cancer, Parkinson’s disease, Alzheimer’s disease and spinal cord injuries a greater thrill than to be able to rejoice that the debates around stem cell research are finally over, and “the Holy Grail has been achieved,” as Charles Krauthammer put it in an astonishing piece in the Washington Post. Krauthammer said that last week’s announcements means that George Bush was right, that we have now found a way to create “a magical stem cell that can become bone or brain or heart or liver” without using human embryos.

It is not true. It is not even close to true. The new “induced pluripotentiary stem cells” (IPS for short) will be powerful tools for scientists studying the mechanisms of human diseases in their laboratories, and there is no doubt that this is an important scientific event. But these cells cannot be used to treat human patients in the clinic, because they were created using genes and retroviruses that can cause cancer in humans. Moreover, even if safe ways of producing these new IPS cells are found, no one yet knows the extent to which they will behave like true human embryonic stem cells. To suggest, as Krauthammer and others have, that we now have no need to work with stem cells created from embryos is to say that we can put aside the research that remains the most promising and important. It is a conclusion based on political, not scientific, considerations.

It is crucial to our ultimate success to allow wide access to all of the stem cell lines that have already been created from embryos as well as to continue to create new lines for comparative and other purposes, including the research that can only be done with human embryonic stem cells. To gain the most benefit from the new discoveries, it is urgent — as urgent as it was before these announcements — that the current federal restrictions be lifted. For many kinds of research, there is still no substitute for actual human embryonic stem cells, and these new discoveries simply don’t change that fact.

The greatest loss of all would be if these exciting new discoveries were allowed to create the false belief that the kind of research opposed by the Bush administration — research involving actual human embryonic stem cells rescued from frozen embryos that would otherwise have been discarded — was no longer necessary. If it becomes even harder to fund human embryonic stem cell research in light of these new discoveries, they will, ironically, end up being as much a roadblock to scientific progress as an advance, which is something the researchers behind them never wanted to see happen.

Senator Tom Harkin of Iowa once said that science is like looking for a treasure behind closed doors that can only be opened by experiment. Since we don’t know which door conceals the treasure, it is important to open as many as possible. “It is like you have got 10 doors that are closed and you do not know behind which door may lie the answer. If you [only] look behind one door, you have got a 10-percent chance of finding that answer,” he has said.

If only science were just a matter of opening a single door. Doing all we can to further human embryonic stem cell research will advance the search for cures of the major diseases of our time, and it should still be the number one priority for researchers, as well as for the private funders who today are the only sources of support for this vital scientific work. It is far too soon to call “Game Over” in the stem cell debates.

:: :: :: :: :: :: :: :: :: ::

Read my full review on new stem cell books in this month’s issue of Nature. Navigate to the review under the news tab on Nature Reports Stem Cells.

¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤

by Christopher Scott

It’s been a couple of months since I’ve updated TSC’s Read page, but if you’re looking for holiday gift ideas or hankering for a good read about stem cells, you’re in luck. Two new titles join a growing group of volumes examining stem cell research through different lenses. For an account of the controversies surrounding patents and law, read Russell Korobkin’s new book, Stem Cell Century (Yale University Press). It explains the profound effects of law and policy on stem cell research and regulation. Korobkin, a UCLA professor of law, demonstrates how a formerly quiet corner of biology has exploded into new realms of intellectual property, commerce and international affairs. My favorite chapters focus on stem cell patents and the potential paybacks for big science initiatives like CIRM. Deeper dives into the ethics of buying and selling human tissues, and how they impact egg donation, are worth reading. A small quibble: Stem Cell Century is uneven in places, switching among lawyerly, academic and journalistic styles.

The editors of Fundamentals of the Stem Cell Debate (Kristen Renwick Monroe, Ronald B. Miller and Jerome Tobis, eds. University of California Press) offer a book addressing the complexities of stem cell research and the swarm of disciplines busily dissecting its scientific and medical impacts: law, ethics, policy, and commerce. And who better to ask to write chapters than a group of scientists and academics that do it for a living.

There is much to like here because the authors don’t hesitate to tackle difficult subjects, such as what we should do about the ethics of clinical trials: the first experiments that will put stem cells into people. This subject is uncharted waters for biomedical ethics, and the research and comment is just emerging. Fundamentals gives you a peek at what scholars think, especially how scientists, unaccustomed to defending their work in very public ways, articulate arguments for supporting an area of biology that is, for all intents and purposes, on a tear.

How can someone navigate among the profusion of books on stem cells? My advice is to read two or three. Recent releases include books on activism, politics, religion, ethics, popular science, and for the adventuresome reader, a couple of game efforts at writing introductory texts.

On the last point, there are a few reasons we don’t yet have a good introduction for high school and university curricula—something I bump up against when planning my classes at Stanford. First, the field is still pretty new. Second, the subject cuts across the tried-and-true developmental and cell biology texts—faculty aren’t so willing to take a chance on something new. Finally, a good introduction should include chapters on ethics, law and society. A hybrid may not fit neatly into a publisher’s marketing plan. But I predict we’ll see the first textbook by a major press soon enough.

A huge month. A huuge month.

The Vatican tries to gets its arms around the human embryo. A New Jersey vote defeats stem cell funding. The California Institute for Regenerative Medicine struggles to exit the spotlight and enter the grants-making business: David Jensen explains. Thanks to James Thomson and Shinya Yamanaka, we welcome new arrivals to the stem cell family, joining a dewy colony of cloned monkey cells. Aww, cute. A private stem cell bank storing menstrual blood says the cells found there “demonstrate compelling promise to transform commercial therapies.” We’ll see about that. Geron, a leading embryonic stem cell company, reports in the Journal of Neuroimmunology that its embryonic stem cell line provokes only a minimal immune reaction in laboratory experiments. Hillary Clinton, in a moment of clarity, appoints Colorado Rep. Diana DeGette as a health adviser. Fred Thompson, in a fuliginous fugue, cites the widely discredited Prentice List of 73 Stem Cell Treatments. India finally issues its draft guidelines for stem cell research.

Scott Dylla is a senior scientist at Oncomed Pharmaceuticals, a small biotechnology company focused on developing novel therapeutics targeting cancer stem cells. He trained at Stanford University with Irving Weissman.

¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤

by Scott Dylla, Ph.D.

Seven years into the 21st Century, cancer continues to be the #1 cause of death worldwide. Although therapeutic response rates and time to progression have dramatically improved, long-term survival has not changed for most, if not all, solid tumors such as those of the lung, breast, and colon. Past decades of cancer research and drug development have largely considered all tumor cells equal in status and potential for harm. This is no longer the case, as rare subpopulations of tumor cells are being identified as responsible for fueling tumor growth. These cancer stem cells (CSC) appear more resistant to chemotherapy and radiation than most cells within the tumor, explaining why tumor regression following such therapies is so common. Furthermore, because newer therapies composed of antibodies or small molecules have been developed against bulk tumor cells and not the CSC population, it is unlikely that cures for cancer will be imminent until the scope of attention is focused on the CSC population itself.

Normal stem cells serve to support tissue growth and maintenance over the lifetime of an individual. Cancer stem cells, on the other hand, appear to be black sheep of the stem cell family and best resemble a normal tissue-specific stem cell gone awry. Although normal cells are generated, the growth rate and cell organization are highly abnormal because the CSC parents are generating too many offspring; ultimately resulting in masses of dysfunctional tissue. Because CSC have been differentiated from the majority of cells within a tumor that can be likened to branches of a tree, novel therapies with better efficacy will likely be aimed at the roots of the tumor (i.e. CSC). Realistically, the next generation of cancer therapies will target molecules on the cell surface, or within the cell, that CSC utilize to proliferate or survive as long-lived stem cells. Ideally, these therapeutic targets will not be expressed on normal stem cells such that there will be little damage to normal tissue.

Yet, the identification, isolation, and experimental manipulation of CSC from solid tumors poses major obstacles. As might be imagined, ripping cells away from their neighbors, upon which they are largely dependent, is no easy task. Developing assays that further allow CSC manipulation to learn about their biology is even more difficult. I’m often asked when there will be a “cure for cancer.” My answer is often that the term cancer encompasses many diseases and the war will be won in a progression of smaller battles. I am encouraged by my daily work with CSC that commonalities can be exploited to vastly improve not only treatment, but detection of cancer at earlier stages where therapies may be most beneficial.

Eric Chiao’s post about model systems reveals how important these new iPS discoveries could be for hundreds of stem cell laboratories. He says (with tongue firmly in cheek) that disease-specific lines can be made quickly, in as little as a few weeks. The beauty of the Yamanaka and Thomson methods are that they use standard gene manipulation techniques, which means not only do they go quickly, but they can be rapidly adopted and replicated by laboratories anywhere. I figure that research directors have already handed off the papers and supporting materials to graduate students and postdoctoral fellows with these simple instructions: “try it, and get it to work here.”

This means that in short order (assuming all goes well and the methods can be repeated) we’ll see a profusion of reprogrammed lines using every imaginable kind of cell: different cell types and ages, along with normal and diseased cells—even cells from specific genetic populations. The problem facing embryonic stem cell research is that embryonic lines are in short supply. This problem is sidestepped by putting iPS lines in many labs, and then comparing them across research projects.

No one knows whether these new cells will be as useful as embryonic stem cells. Researchers will have to compare them to existing lines, and we know that even embryonic stem cells lines differ (See TSC’s Three Reasons for More Lines). They have to prove their usefulness in the laboratory—they may be good for some experiments but not for others. It is quite possible that iPS lines may not behave the same from one lab to another. And, the technical hurdles must be overcome before they can be used in the clinic. The lines were made using genes and retroviruses that can cause cancer in humans (see TSCs Gene Therapy and Stem Cells). This might be solved by putting the genes into a skin cell, reprogramming the cell to an embryonic state (or other desired cell type), and then taking the genes out with a technique called Cre-Lox.

The fact that we’ve got a new kind of cell to work with only underscores why we must push forward with embryonic stem cells and do the experimental comparisons. Embryonic stem cells are the gold standard. Good science dictates that we use that—and no other—before we declare a new standard.

Eric Chiao is a scientist at Stanford’s Institute for Stem Cell Biology and Regenerative medicine. Along with his research, he teaches in Stanford’s Center for Human Embryonic Stem Cell Research and Education, and was responsible for deriving its first embryonic stem cell lines.

¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤¤

by Eric Chiao, Ph.D.

When the news about the new discoveries first hit, I immediately wondered how it would effect me. I realized that there would be a flurry of disease specific induced pluripotent stem (iPS) cell lines. Then I started thinking about how it would be politically manipulated to restrict human embryonic stem cell (hESC) research. I spent most of my mental energy devising philosophical arguments for the continued support of hESC research.

On Tuesday, I got an e-mail from a friend, who forwarded me Shinya Yamanka’s Cell paper. He asked jokingly how long it would take me to get some iPS cells. I replied somewhat tongue-in-cheek that apparently it would take about 20 days (Yamanka reported seeing colonies of embryonic stem cells at 25 days).

Since I’ve sent that reply, I’ve come to believe that we are one the verge of a new phase in biomedical research. As basic researchers, we exploit the power of model systems (using lower animals such as worms, flies and mice) as much as possible. In the past, basic research with mouse embryonic cells trumped human embryonic cells because we could easily mutate and change the mouse genome. The hope for human embryonic stem cell research was based on translation: the (relatively) minor differences in regulatory pathways between mice and humans, and eventually, from the lab to the clinic.

When Yamanka announced he had made the first mouse iPS cells in July, it was cool, but you could already manipulate the mouse genome, such as using “knock out mice” to render a gene inoperable, and then observing the effect. So it didn’t change the direction of anybody doing research outside of the “reprogramming” field.

But a human “model system,” has, until now, been out of reach for basic biomedical research. What we have in humans is a huge population of pre-made mutants—a wide range of genetic predispositions for diseases and disorders, such as cancer and aging. This makes us the species of choice for devising medical treatments.

It’s true that technical hurdles must be overcome before we can use these cells for tissue replacement therapies. But the fact that human iPS cells can presumably make all the normal adult cell types means that we now have within our grasp (to borrow the mouse lingo) all of the “constructs” to make embryonic stem cell lines for every human genetic disorder….in just 20 days. ; ) These “diseases-in-a-dish” will become important tools for discovering drugs and understanding human disorders and development.

We may see the ascendance of these new discoveries as a model system, on par with the path-breaking work made in mice made over the last twenty-five years.

But only much faster.

:: :: :: :: :: :: :: :: :: ::

This post is part of today’s Google News. See my comment in SFGate, USA Today and the San Jose Mercury News (registration required).

by Christopher Scott

The news that scientists have made human embryonic-like cells by reprogramming skin cells shouldn’t overshadow the fact that these exciting results rely on, and will continue to rely on, our understanding of human embryonic stem cells. The guild of stem cell biology is agnostic to cell type: it makes no distinctions among adult, embryonic and now “induced pluripotent stem cells.”

In order to utilize our knowledge for future therapies, discoveries from every corner of biology must be freely shared and fully employed. The genes used by these labs are present in human embryonic stem cells: an instance of how one area of biology informs another. One of the lead reprogramming experts, James Thomson, is known for his discoveries with human embryonic stem cells. And, this week’s report about cloning monkey cells is a major step towards making custom-matched embryonic stem cell lines for research and medicine. Not surprisingly, Dr. Thomson trained at the same Oregon institute that reported the monkey cloning discovery.

The interrelatedness of these discoveries, and the histories behind them, is testament to why we must freely pursue all avenues of stem cell research.