Fighting for the Right to Clone

We have decided that as soon as we raise £450 I am buying a laptop to build a website for an international campaign in support of Declan's petition to the UN on research cloning of embryos and stem cells, which will be uploaded in free space. For the past few weeks, half the computers in our local council's Idea Store Whitechapel library have been turned off as result of faults (last Saturday I even had difficulty booking a computer for Sunday) and things don't look good for September when everybody is back from their break. We don't believe we can rely on the library computers to do our emailing and work, and so we are switching to the campaign instead of waiting until we are off the street – we are giving ourselves two weeks to have the campaign on the internet (although we won't go public to patients' rights organisations until we have a sufficient number of distinguished signatories, and hopefully the endorsement of scientific organisations). Central to the campaign are applications of embryonic stem cell technology: for example, the growth of human blood for transfusion (see previous blog) and the generation of retinal pigment epithelium cells to treat human blindness (see below). The campaign will also expose that an egg-payment ban is hindering therapeutic cloning research (San Francisco Chronicle "Scientists: Egg shortage hurts stem cell research").

Robert Lanza

On 19 August, Discover magazine published an interview with Robert Lanza, Chief Scientific Officer of the biotech company Advanced Cell Technology in Massachusetts (who is an early signatory of Declan's petition), under the title "Fighting for the Right to Clone", with the subtitle "Stem cell and cloning guru Robert Lanza has battled the Catholic Church, the White House, and violent protesters". As mentioned in the previous blog, last week Lanza announced that his research team had devised a way to grow large quantities of blood in the lab using embryonic stem cells, potentially making blood drives a thing of the past. The Discover introduction reveals that Lanza is close to delivering cellular therapies that might reseed the immune system, heal damaged hearts, even save limbs. "Yet for almost 20 years government policy has kept his innovations literally on ice. He has been called a murderer for tampering with embryos, and personal threats were so common at one point that he believed he would be killed."

It is no wonder, Discover says, that Lanza "would lead the charge into medicine's most controversial turf: the creation of cloned embryos for therapy and the engineering of spare human parts". The value of therapeutic cloning has long been clear to Lanza, who did his early work with South African heart transplant pioneer Christiaan Barnard. Starting from those early days, Lanza understood that the barrier to tissue transfer was rejection by the recipient. From an entire organ to a dose of embryonic stem cells, if the tissue's DNA came from anyone else, the transplant would be rejected without the aid of harsh immunosuppressive drugs. "The treatment could be worse than the problem," Lanza found.

Around 1990, when Lanza was still at UCLA, he was approached by BioHybrid Technologies in Shrewsbury, Massachusetts, and it was while working for BioHybrid that he learnt about Dolly, the sheep cloned by Ian Wilmut, Keith Campbell (both signatories of Declan's petition) and colleagues at the Roslin Institute in Edinburgh, Scotland. "Aha! That's it," he says he said, adding that if you can create an embryo genetically identical to the adult - that is, a clone - you can harvest immune-compatible cells to replace any tissue you might want without fear of rejection. "My idea was to clone the sick individual, not for reproduction but for therapy," he says. "The stem cells produced through this therapeutic cloning would, like other embryonic stem cells, be capable of developing into many cell types and serve as a repair system for whatever part of the body required replenishment at the time. You solve the rejection problem, and you have unlimited amounts of tissue."

In 1998 Lanza learnt that there was a cloning company right up the street from BioHybrid that was "the top in the world", called Advanced Cell Technologies, or ACT. But before they would hire him they gave him a task "that was like bringing back the witch's broom". There was a question about whether the National Institutes of Health would allow the work, Lanza says. "Even though this was for therapy and not reproduction, it still involved cloning embryos, and the public was totally against it. Many considered it murder. So I was asked to get all the Nobel laureates in the country to sign a letter to support embryonic stem cell research, addressed to Harold Varmus, the head of the NIH [National Institutes of Health]." The effort was published in Science, and a few months later, many college presidents also signed on. (The letter published in Science on 19 March 1999 can be read here; and another letter, co-authored by Lanza, published by the Washington Post on 21 February 2001, and signed by 80 Nobel laureates, can be read here.)

At the time, Lanza recounts, ACT was a subsidiary of a poultry genetics company, doing work in agriculture. "When I joined they made the move from animal cloning to human therapy, and we knew we would get hit, big-time. I may be the only person who's had the [Catholic] Church, the pope, and a couple of presidents condemn my work. At one point we had bodyguards here. There was a bombing up the street; then a doctor at a local in vitro fertilization clinic was targeted. I didn't think I would be alive for more than a few years."

Lanza describes the original groundbreaking work at ACT: "We injected human DNA from an adult cell into an egg from which the nucleus had been removed. We managed to clone early-stage embryos that grew to four or six cells in size. This was obviously far short of getting stem cells, which require a blastocyst [an embryo with a larger cluster of cells]. In fact, even to this day, a decade after the cloning of Dolly, scientists still have not cloned human embryos developed enough to generate patient-specific cells."

Lanza has been exploring other ways of producing patient-specific cells. "We recently published a paper on a cell we created called a hemangioblast, which exists only transiently in the embryo but not in the adult. I think of them like unicorns, these elusive cells that we had hypothesized and sought for years. With the ability to become all of the blood cells--including your immune cells, red blood cells, all of your blood system, as well as vasculature--hemangioblasts have been biology's holy grail. What we discovered is that we can create literally millions or billions of these from human embryonic stem cells. Now that we have them, we are harnessing, for the first time, one of nature's early, most profoundly powerful cellular building blocks. The point is, we can use transient, intermediate cells like hemangioblasts as a toolbox to fix the adult so you don't have to have limbs amputated, so you may not have to go blind, to prevent heart attacks. We can direct their development into different cell types by adding certain molecules to them as they divide."

Lanza recounts that a police officer visited him four years ago because he had a 16-year-old who would go totally blind in two years; Lanza had just published a paper showing that they could create human retinal pigment epithelial cells capable of restoring visual function in animals. "By the time he finished his story, I was almost in tears because we had these cells and they had been frozen at that point for nine months," Lanza says. "We didn't have $20,000, which is what we needed to do the preclinical studies required for working with people. At that point, our phones had been turned off. We didn't have a fax machine. I couldn't even afford bottled water for my pipettes. The point is, there is just no funding because basic research is generally funded by the government and the government will not fund stem cell work." (An article dated 23 September 2004 titled "Successful Generation of Retinal Pigment Epithelium Cells to Treat Blindness Reported in Cloning and Stem Cells" can be read here; Lanza's Cloning and Stem Cells paper here.)

So what does Lanza think these technologies portend for human longevity? "It turns out that the human life span plateaus as it approaches a roof of about 120. By eliminating infectious diseases, some chronic diseases, and cancer, we can get the life span past 100. I think with tissue engineering we can patch you together like a bicycle tire, replacing a kidney with a kidney and a heart with a heart, to about 120 years. That was always my thinking: That was the limit. But with these hemangioblasts, I now have questioned my own rules. These cells can go in and fix the damaged tissue inside, almost like nanoparticles. We may be able to do the same thing with similar cell lines for neurons, where we can repair the damage in the brain itself. So if it continues the way it's going, we may break that ceiling, like breaking the sound barrier. I'd be very hesitant to put a lid as to where longevity is going to go."

"Rather than curing disease, we're trying to get around theological problems," Lanza says. "It's not what I signed up for in medical school. I can't tell you how many times I've thrown my hands up and said, 'Enough, I can't take it anymore,' but then I'm back the next day. We're crippled, but they can't stop us forever." He says that it's just a shame that the research has been held up so long. "We're living through a paradigm shift. People are going to look back at us and say, 'They used to cut people's legs off.' Then they'll just give an injection and the blood flow will be restored and the limb saved. If I were a patient and I knew I was going to have my leg cut off and something could be done, I would be demanding it. But most people, even most scientists, don't realize what we're capable of. I realize it because I'm doing the work and I can see what's possible before my eyes."