Stem Cells and Digressions.

By Phyllis Draper (aka Grammy)

A quick note about my grandmother and the author of this essay. Her name was Phyllis Draper and she had Parkinson’s Disease for 40 years. She wrote this in 2006, but as you read - it will feel very applicable to today. It is long, but I highly recommend taking the time to read it - it will put you at the forefront of understanding the world of Biology today.

My grandmother swam every day until she couldn’t, then she walked two miles a day until she couldn’t, then she walked as far as she could until she couldn’t. She always showed up with a smile when she fell and a “Whoopsy”. She was not a scientist. She was a patient, and it is hard to read this and not believe she knew more than anyone on the topic of Parkinson’s.

I’ve read this essay now hundreds of times, it is hopeful of the transition from chemistry to Biology for the cure of Parkinson’s. It discusses the social, religious and scientific debates of stem cells — it even has a digression, which is a quick sci-fi concept she wrote with a great sense of humor.

This essay has become the core thesis of Boost VC for Biology over the last 3 years. Unfortunately, my grandmother passed away before any reality of stem cells revolutions emerged — due to many forces, some of which she describes.

I believe today we have the tools to cure everything, and at Boost VC, we want to be a part of that.

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Stem Cells and Digressions.

For the past century, most of the advances in medicine have been based on the use of chemistry. The new approach is to use biology to attack diseases by using the body’s own building blocks, called stem cells. This marks a new and very exciting era in medicine, and has the potential to cure a range of diseases that presently afflict roughly half of the world’s population.

Stem cells are the basic building blocks of life. A fertilized human egg, called an embryo, contains cells that have the ability to divide for indefinite periods, and eventually grow into all 200 or so specialized cells in the body. The body also produces a certain number of stem cells that remain active throughout most of our lives but turn into specific cell types such as skin and bone cells. These are called adult stem cells. They are already proving useful in treatments of certain cancers—those which need bone marrow transplants, for instance. No one knows exactly how most therapies can be developed, but scientists know that the continued study of stem cells will reap many benefits for the world in ways which as yet we can only imagine.

Therapeutic cloning, as distinguished from reproductive cloning, also known as somatic cell nuclear transfer, has as its goal to create a new embryo from cloned cells and to use these embryos for research. Thus cloning has its place in the stem cell controversy. And it is the most controversial of all controversy surrounding stem cells.

Most of us non-scientists were not aware of stem cells until relatively recently and today they have become among the most controversial subjects around. People who under ordinary circumstances could be counted on for their rationality and solid judgment, upon entering into a conversation about the efficacy or moral right of the study of stem cells, become totally unpredictable. Much of the debate, both scientific and ethical, has focused on its two potential applications: Stem cell cloning for reproductive purposes and stem cell cultivation for the purposes of research.

The term stem cell was the name given by Gail Martin, a researcher at UCSF who in 1981 isolated some cells from a mouse embryo, and named them stem cells because she discovered nearly every type of cell stemmed from them. Stem cells can be found in embryos, and in adults, although the procedure for harvesting adult stem cells is more difficult than finding them in embryos. Almost 20 years after the discovery of stem cells in mice, researchers found equally versatile stem cells in human beings. This spawned a running controversy concerning cloning and the ethics of tampering with nature, and in a premature backlash, caused the U.S. government, in 2001, to declare that to work on cloning was a criminal offense. The government did not disallow stem cell research for purposes of research, however, although they limited the research to a very small allotment of cell lines to study, which is what prompted California’s Proposition 71. But I’m getting ahead of myself.

Stem cell cultivation is on two tracks. In early human embryos there are stem cells that can in theory grow into any of the body’s tissues or organs. Human embryonic stem cells have to be grown for nearly five days, and obtaining these cells has in the past meant that the embryos must be destroyed. In adult stem cells, there is no need to destroy an embryo, which makes the science less controversial. But some scientists believe that adult stem cells are more limited in scope, and good for only a limited number of roles in the body. Therefore these experts are not persuaded that the use of adult stem cells will be as therapeutically useful over the long term as the embryonic stem cells, which hold out great promise for curing diseases. There has been considerable success already, however, with certain treatments involving adult stem cells, such as bone marrow transplants. In the process of experimenting, scientists have also discovered stem cells in the brain, as well as the bone marrow, also in blood vessels, skin, and liver. Though they are much more difficult to harvest, there is still room for hope that these stem cells will prove to be even more successful in the long run.

People who, on either ethical or religious grounds, see the embryo as a full human being object strenuously to what they see as the murder of a potential baby. Others feel equally strenuously that it is cruel to deny the research money and support for what could be a lifesaver of another kind: The potential to treat, and even to cure, certain scourges of the population. Unfortunately, to weigh in on one side against the other in this case is fraught with choices one should never have to make.

On October 11, 2005, an article appeared in the New York Times that seemed to be a breakthrough for those ethicists who maintain the belief that a human embryo is the same as a baby because it can grow into a baby. Two scientists, one from Harvard, and one from MIT, think that they have found a way. Despairing that the government would not fund anything with an embryo in the title, Dr. William Hurlbut from Stanford explains this new process: “What I’m suggesting is creating something that never rises to the level of a living being. No embryo is ever formed. It’s not a human embryo if it doesn’t have the potential to develop into human form.” Instead, he called this a “biological artifact.” In order to make this artifact, first one separates the genes from the adult cell from among those that are needed for the full development of an embryo, and then the altered cell is added to an egg. The eggs could come from unused eggs at fertility clinics. Or, the doctors say, the eggs might come from women’s ovaries collected during an operation such as a hysterectomy. In fact these researchers claim that further study might lead to being able to do without the egg as well, by adding proteins to the stem cell in the right amounts.

Many people, including John M. Haas, president of the National Catholic Bioethics Center, and Edward Whelan, president of the Ethics and Public Policy Center, agree that this discovery has forged a way for ethicists who have previously been averse to any research on stem cells to accept the fact that this study would not affect the birth of any baby. Therefore it was presumed that the naysayers would be whole-heartedly behind stem cell research from this point forward.

Several days later I read in the San Francisco Chronicle that this was not the case. Many people were not convinced that the new method was anything more than a thinly veiled attempt to call the experiment with embryonic stem cells by another name. A biological artifact to them was still an embryo. The federal government is in this camp, unfortunately for those who wish to accelerate study in the U.S. It would appear that any attempt to destroy what is considered by these people a human being from the time of its conception will be met with implacable resistance. There has been no appreciable attitude change from early in this century.

The controversy is still alive today. For this reason, the research has not been accorded the money and go-ahead from the national government, and the state of California has taken matters into its own hands by passing a proposition that allowed funds ($3 billion) for the purposes of stem cell research. The University of California in San Francisco and Stanford University are both at the forefront of that research. However, California is presently involved with lawsuits that threaten to make the proposition—passed over a year ago—invalid. The two universities, having gathered together an impressive lineup of talent from all relevant disciplines, have had to apply for private grants in order to keep them afloat. Once again they have been delayed in their search for a breakthrough that will surely change the face of medicine forever.

Cloning has become the most frightening of all stem cell controversy. Though in literature and entertainment the topic has always been popular, in real life, the prospect of cloning humans is too science fictitious to contemplate, but we do contemplate it, nevertheless. Recently, Science Magazine carried the story of a Korean scientist, Dr. Hwang, who claimed to have cloned a dog, having spent many years and thousands of dollars in the effort. Americans had been experimenting with the cloning of dogs for years, without success, but they were eager to hear how it was done. It was considered by scientists to be the Mt. Everest of accomplishments and held promise for therapeutic breakthroughs, because dogs’ diseases are the most like human ones. It was acknowledged even at the time that it’s far too soon and complicated to clone a favorite dog pet. Yet no one could imagine how many windows were opened for the future. They were amazed and impressed. The Koreans were very proud of their accomplishment, and hailed Dr. Hwang as their number one citizen.

On January 10th the news came that Dr. Hwang and his staff had falsified all his cloning experiments. He claims to have been the first to clone a human cell by inserting a adult cell’s nucleus into a fertile egg to make embryonic cells. With this method he claims also to have treated 11 people in a first step towards therapeutic treatment with their own regenerative tissue. If this were true, there would indeed be reason to celebrate, and in fact Dr. Hwang would well deserve the postage stamp that Korea issued in his honor. However, his peers also believe that he falsified the evidence of cloning of Snuffy the baby Afghan hound.

Other animals have been cloned, with varying degrees of success. In March of 1999 four calves were created using stem cells from a prize Japanese bull. In March of 2000, a company hoping to generate organs for humans cloned five piglets. A cat named CC, for carbon copy, was created in 2003. Of course we are aware that every identical twin or triplet is a clone, a natural one. But these cloned animals have not proven to be as healthy as the originals, including Dolly the sheep, the first cloned animal, who has developed bad arthritis, although her “mother” shows no sign of it. Most scientists would like to tone down the controversy concerning stem cells, but it doesn’t seem to go away. It seems that no matter what they do in the way of stem cell research, it’s sure to displease somebody.

What all agree upon is that the U.S. is falling farther and farther behind in this new field of therapy. Meanwhile people on both ends of the spectrum of opinion remain adamantly convinced of their own point of view. The people in the middle, however, are much more flexible on the subject of stem cells, and their opinions vary when questions are asked in different ways. This is a hopeful sign.

One remembers the eugenics movement of the early twentieth century, in California. The eugenicists had the idea to create a master race. A certain Mr. Goethe felt that animal breeding concepts would be possible to employ on humans. The eugenicists advocated sterilization of immigrants and tough border controls, with Nordic purity as their goal. A true California dream for a while, the idea was smashed with the advent of Hitler and his master race, which demonstrated the horror of ethnic cleansing, and lost Mr. Goethe his followers.

I remember being very disturbed when I first heard about Dolly. That one could clone a sheep meant that—gulp—perhaps humans would be next. I found a short story I had written back then for fun and I include it here as a not-so-serious digression. It depicts a world full of emasculated men due to the loss of their reproductive usefulness. On the subject of cloning, it stars a clone of Arnold Schwarzenegger, our present governor.

Cloning

Last night, in the packed ballroom of the Marriott-Hyatt Hotel in Abilene, Kansas, Arnold Schwarzenegger C5 blew away the competition to become the winner of the Boy Toy of the Year Award for the second straight year. In a stunning finale, after the obligatory promenade in the Bathing Suit competition, he struck a dramatic pose, displaying his vast musculature to a rapt audience, flexing seductively to the music of Claude Debussy. He was accorded a standing ovation.

Many people felt that A.S. Clone 5 had already assured his victory the previous evening with his strong performance in the Talent Event—in which he gave a recitation of Robert Browning’s love poem “How Do I Love Thee” while standing atop a burning automobile and fighting off a horde of killer ants.

A.S. Clone 5 traces his ancestry in an uninterrupted ribbon of DNA to his pre-Clonial forebear Arnold Schwarzenegger, who was conceived in the scatter-shot manner—at the time the only known technique for procreation. Providing no guarantee as to size, gender, coloring, or intelligence, this method rarely produced perfect specimens. Pioneers in the Clone industry on the lookout for prototypes discovered in Schwarzenegger that rare miracle of perfection, and secured his Clonial potential, and all rights thereof, in perpetuity. Thus, despite all the piracy and experimentation that plagued the industry’s early years, his DNA has remained unchanged and completely pure. If there were ever any doubt that this was so, the company points to the heavy German-Austrian accent still prominent in A.S. Clone 5; it is a vestigial characteristic—as A.S. Clone 5 has never set foot in Austria or Germany.

In a far-ranging interview after the award ceremony, A.S. Clone 5 entertained questions on a number of topics, and became particularly animated when discussing his lineage, long a source of great pride. “My illustrious ancestor five generations ago,” he said, “although he was just like me…hell, he was me… this guy lived in a completely different world. There was no way a woman could get by without a man to start the fetus-making process. Men were very important, in fact, they were essential. They were so powerful that in those days they ran everything. Their attitude was called macho, or machismo, I believe.” He then explained, in answer to the question posed by Walter Cronkite Clone 5, as to what the women’s role was back in pre-Clonial days. A.S. Clone 5 is known to be a student of history, so it was not surprising that this question elicited an expansive answer. “Women,” he said, “were treated about the way we are treated today. They didn’t run things the way they do now. There were almost no women in the government, let alone presidents of the country. Men today are pretty much sex objects and pleasure providers, and I for one don’t mind this at all,” he added with a grin.

Although he claims to be in sympathy to some extent with the reactionary Back to the Basics party—who want to re-associate procreation with recreation and bring the man’s sperm back into work as well as play—he wonders whether “people will be willing to take such a crap shoot approach to the reproductive process after all these years of cloning.” On the other hand, he is known to be very much offended by the excesses in women’s fascination with the male body. He explains the consequences of sexual harassment in the workplace: “It keeps men from wearing tight pants, because we’re subject to so much harassment and crude remarks about our measurements and backsides.” Overall, however, A.S. Clone 5 enjoys the role of pleasure provider, and looks forward to another year of Boy Toy activities and appearances around the country. His first appearance will be to promote the newest Ken Doll, whose measurements are said to be modeled after his own.

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More Digressions

Several novels that I have read lately are science fiction of a higher order, and posit three different anti-utopias or dystopias. Each one leads into areas that really surprise. The first one is called The Slynx, a Russian novel written by the niece of Tolstoy, Tatyana Tolstaya. This science fiction tale is set in Russia some two hundred years after the bomb has fallen. What is left of civilization are merely remnants of a culture so torn that it is disassociated from any world view, values, or behaviors of the past. The ruler has got hold of some books and plagiarizes from them in his speeches, mixing styles as varied as nursery rhymes and tax reports. This is carried out very successfully as his subjects, not permitted to read books, are always very impressed by the words, no matter what he says. He is a god to them. His name is Fyodor Kusmich Glorybe. Among his many talents he claims to have invented fire. A couple of the elders are misfits in that society but are the only ones left who have managed to hold on to bits of civilization. In their midst live humans who are saddled with “consequences,” which is the name they give to the genetic altering that has taken place due to the bomb’s after effects. Unlike cloning, which in our time offers possibilities to create perfection, these people suffer from a scourge of bizarre alteration. Our narrator, Benedickt, has a tail. His girlfriend—later his wife—seems perfect but for her hooves, a “consequence” that she shares with her parents. Others have really bad “consequences.” One of Benedickt’s friends is a very nice girl but she has a beak sticking out of her forehead, and only one eye.

Rats are the mainstay of the economy, and the principal source of food. Most meals the author describes have a rat dish in it. Like other science fiction tales that hold a message, The Slynx shows us a world that is the direct result of man’s follies, in particular and foremost the hydrogen bomb. The book is often very funny, but its underpinnings are at all times deadly serious. We are compelled to wonder if our “consequences” could be similarly devastating. The slynx, by the way, is a dreaded monster who awaits people in the woods. We think he is not real.

It was sheer coincidence that the next book I chose to read was also a post-apocalyptic science fiction novel, this one called Oryx and Crake by Margaret Atwood. Against a background of massive destruction that may have also come from a bomb explosion, we find that science has gone far beyond what is good for us. Scientific cabals had formed and kept secret from each other. The most powerful group rules everything at this point and is headed by Crake, who is in the business of cloning humans. The narrator is Snowman, a ragged, dirty man whom we first find sitting in a tree wrapped in a dirty sheet. He is starving and lonely, with only his memories to keep him in touch with a past that bears some resemblance to today, but none to the world he now inhabits. In that earlier world his name was Jimmy. We learn that Jimmy had friends and playmates. His good friend was Crake—who grew up to be the biggest cloner and manipulator of clones and people. Crake has become mad during his lifetime of cloning in his sacrosanct factory, where one product is slave girls (Oryx was one of these). In fact, so many types of cloned individuals were invented that they became unrecognizable as humans. Snowman’s only companions are the perfect, green-eyed Children of Crake, who are dopey clones. The book speaks to today’s reverence for science, whose remedies we count on to cure just about everything. In this case, the powerful moguls of science are the villains in Margaret Atwood’s future world.

In Never Let Me Go, Kazuo Ishiguro writes a story that seems to be a fine boarding school saga at the start, but gradually, with a few harbingers of unease sprinkled into the story line, its horrors are revealed. We are introduced to the private school where children are raised in a benign atmosphere without any contact to the outside world. They have no families. Their “guardians” are their teachers. Miss Lucy is one of their favorites. It seems a fine, loving orphanage. One day, when the children are around 15 years old, Miss Lucy tells them of their special role in life. She is prompted to tell them because she overhears two of the boys making plans about what they’d like to do when they leave school, and she feels pity for them. Only on page 82 does the author tell us what is going on behind what seemed to be an idyllic school environment, and what is behind all the vagueness of the questions that had come up from time to time. The children are clones, who, like the pigs of today’s cloning efforts, are created solely for harvesting their organs. One group is meant to become the Donors and the others are to be their Caretakers. The Donors are to be ready to “donate” organs when needed. The maximum number they are asked to give is four, though often Donors die before “donating” all four.

The story tells of genetic manipulation for a cause, which though noble (we need organ transplants), treats human life as just so much clay to serve human ends. It is never clear whether this is a scientific experiment or a moneymaking scheme. The most heartbreaking thing of all is that some of these clones have emotions, which apparently have not been bred out of them. They have sex (though none can have babies) and develop deep attachments to each other. It is the particular cruelty of this fact that makes the book so devastating.

Reading these books leads one to think about the situation with stem cells today and about how scientific advances can have unforeseen consequences. Certainly the far-right religious folk are vociferous and fiercely against any new stem cell study, claiming that the use of embryos is murder of a human being. Dissenters cite the idea that because of a minority opinion of what is ethical, we stand in the way of progress towards cures for millions of people, thus creating a situation that is, to them, unethical. Somehow I don’t feel that the religious and Republican far-right is concerned about the advancement of science so much as they mind the methods being used. They are still a minority, and there is growing support on the part of other leaders in the U.S. One of these, Governor Doyle of Wisconsin, as part of his campaign for reelection, says he aims to have the research market of stem cells a growing industry by 2015, employing thousands of people and generating $8m, citing that his state was already ahead of most other states in terms of research (California Included) and stands in a good position to surge ahead.

It appears that no one can leave the subject alone. Ever since the Woody Allen movie I saw years ago in which a character was to be cloned from a nose, I’ve found that cloning has creeped up in our literature in science fiction, and in the media. One can hardly ignore it today, and especially in California. The courts here are the battleground between two sides; the state is currently waging a battle to strike down Proposition 71. The proposition as an attempt to circumvent federal restrictions on research involving human embryonic stem cells. The legal maneuvering against initiative represents politics at work, and makes the issue muddier and the outcome else predictable. The California government and the California Institute of Regenerative Medicine, the governing body of the stem cell research, are at loggerheads over certain issues. The state is worried about a loss of revenue due to the fact that the federal tax laws might not allow the state to claim royalties from a private enterprise. They worry that the leader of the institute, who also initiated the initiative, Robert Klein, is not a scientist— although he has collected many noted scientists for the institute. Klein in fact has been criticized by some for having omitted some crucial information to the voters at the time of the voting last year. The state also has a concern about the ethics of using eggs from women who undergo the lengthy process, and are remunerated for their donations. It seems to me that these are negotiable, minor obstacles to what has been referred to as “California’s boldest undertaking of this century.” It’s a gamble, but many people think the rewards would be so extraordinary, financially as well as curatively, that it could change the world.

As you may have noted, try as I might, l am not an objective bystander in all of this. I follow every article and paper I can get my hands on to see how the study of stem cells is progressing, if at all. I rely on my doctor at the Parkinson’s Institute to keep me posted on any progress their scientists have made in connection with my particular scourge, Parkinson’s Disease. So tar, the news is good for the long run. Stem cells might be made to work to augment the dopamine supply that is disappearing from a Parkinsonian brain. That much they know. They also know that it will be a long time before any research is considered safe to apply to humans. So far this experiment has only been proven to work on mice. And there’s a long road to travel from mice to medications for humans. But already there is talk of a medication to prevent Parkinson’s from worsening in patients. This breakthrough may be all I can expect in my lifetime, and I shall welcome it.

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The last paragraph is my favorite.