Use of Cloning to Tailor Treatment Has Big Hurdles, Including Cost
Andrew Pollack
The New York Times
December 18, 2001
That is because the approach, if it works, will involve cloning patients individually in order to develop treatments tailored to them.
"It's too laborious and costly to employ as a routine therapeutic procedure," said Dr. Alan Colman, research director at PPL Therapeutics, the Scottish company that helped cloned Dolly the sheep.
Other leading stem cell companies apparently agree.
For one thing, unless success rates improve drastically, the therapeutic cloning will require a large number of eggs — and women willing to donate them — to make clones for the thousands or even millions of potential patients.
"They're never going to have enough women's eggs available to do it," said Dr. Alan Trounson, director of the Monash Institute of Reproduction and Development in Australia and an adviser to ES Cell International, a company based in Singapore and Australia.
Companies in the stem cell field have to be conscious of business issues because many prospective investors are skeptical about the field. The investors believe the payoff may not come for many years. Even then, many believe, cell transplants will not be as profitable a business as mass producing drugs.
The companies' lack of interest in therapeutic cloning raises questions about how vigorously business leaders, scientists and patient groups will fight to prevent a ban on the practice.
The goal of therapeutic cloning is not to create babies, but rather embryos from which embryonic stem cells can be harvested. The stem cells can theoretically be turned into other types of tissues, like nerve, heart and liver cells, that have the potential to repair organs and cure diseases.
One potential problem is that stem cells are now created from embryos left over in fertility clinics, and tissues transplanted from those embryos may be rejected by a patient's immune system as foreign. With therapeutic cloning, scientists would make an embryo clone of the patient, remove its stem cells and use them to grow needed tissue, which presumably would not be rejected.
But executives of stem cell companies say making such customized tissue will be extremely expensive. "That's a product of one, so the costs are going to be enormous," said Dr. Allan Robins, chief scientific officer of BresaGen Ltd., an Australian stem cell company. He estimated the costs at hundreds of thousands of dollars per patient.
Dr. Michael J. Ross, chief executive of San Diego-based CyThera Inc., said getting such individualized therapy approved by regulators might be hard because of problems verifying the safety of each tissue batch. "The amount of testing you can do for an individual patient is significantly less than if you're doing a drug for a million people," he said.
These executives say there are other ways to overcome rejection that will allow standardized embryonic stem cell lines to be used instead of having to create a customized cell line for each patient. New drugs are being developed to supplement existing anti-rejection drugs, which can have severe side effects. Dr. Robins said 200 different stem cell lines could be made so that virtually every patient could find a close match, to minimize rejection.
Dr. Thomas B. Okarma, chief executive of Geron Corporation of Menlo Park, Calif., said his company was trying to genetically engineer stem cells so they would not be recognized as foreign by immune systems.
Another idea would be to make bone marrow cells out of the stem cells and put them into the patient's bone marrow — where the cells of the immune system are generated — to try to create a mixed immune system, something that has happened with some bone marrow transplants. Then, the tissue could be transplanted and would not be seen by the immune system as foreign.
But Dr. Robert P. Lanza, vice president for medical and scientific development at Advanced Cell Technology, said all those approaches had been worked on for decades, so far without success.
For now, he insisted, therapeutic cloning remains the best option. "None of us would be doing it if there was another way of doing it," said Dr. Lanza, who is an expert on transplant immunology.
Dr. Lanza would not estimate how much treatment using therapeutic cloning would cost, but he said it would be worth it for life-threatening diseases. And he said friends or relatives would donate eggs to make the clones of the patients, just as people now donate kidneys to loved ones. Donating eggs is far easier than donating organs, he pointed out.
In therapeutic cloning, a cell, perhaps a skin cell, would be taken from the patient. The cell's nucleus, containing its DNA, would be put into an egg that had had its own nucleus removed. The egg would be tricked, in effect, into believing it had been fertilized and would turn into an embryo. In about five days the embryo would grow into what is a called a blastocyst, from which stem cells could be extracted. The stem cells would then be cultured to grow into self-sustaining colonies and treated with various chemicals to turn into different types of tissue like nerves or heart cells.
But now the process is inefficient, and it may require 30 to 100 eggs for each patient. In one experiment with mice reported in April, scientists at Rockefeller University started with 1,016 eggs that had already had their own nuclei removed and each had the donor nucleus or cell put in. They ended up with 35 embryonic cell lines, a success rate of about one cell line for every 29 eggs.
Researchers at Monash University, also working with mice, got one stem cell line after starting with 926 eggs. Only 39 percent of the eggs even survived the first step — taking out the egg's DNA and putting in the donor DNA.
It is not clear whether the numbers will be the same for humans. The Jones Institute for Reproductive Medicine in Norfolk, Va., using in vitro fertilization rather than cloning, started with 162 women's eggs and got three stem cell lines. Advanced Cell Technology, in the first cloning of human embryos, started with 71 eggs and got no stem cells because no embryos developed into proper blastocysts. The company tried both cloning and another technique aimed at creating embryos out of unfertilized eggs.
Women who undergo in vitro fertilization typically produce 10 to 15 eggs after days of hormone injections. So if 30 to 100 eggs were needed per patient, more than one egg donor might be needed. Patients needing stem cells might end up competing with couples seeking egg donors.
Dr. Alan DeCherney, a professor at the University of California at Los Angeles and editor of the journal Fertility and Sterility, said a large source of eggs might be the roughly 20 percent of eggs collected at fertility clinics that failed to be fertilized.
But those eggs may fail to be fertilized because they are defective, so it is unclear if they are usable for cloning, he and others said. There may also be ethical problems with using them. And while it appears that fertility clinics get tens of thousands of unfertilized eggs each year, that would be enough for only a few thousand therapeutic cloning treatments.
"We really have to find a way of dispensing with eggs we collect from women," said Dr. Peter Mombaerts, assistant professor at Rockefeller University and a scientific adviser to Advanced Cell Technology. One way, he said, may be to use animal eggs, something the company has tried. Another approach may be to make eggs out of stem cells, since stem cells can theoretically be used to make any kind of cell.
But therapeutic cloning is years from being tried on patients in any case, and by then the efficiency may have improved, reducing both the number of eggs required and the cost of the procedure. Even executives who said they did not think therapeutic cloning would be practical also said the practice should not be banned. At this early stage, so little is known about which technology is best that all options should be kept open, they said.