A professor of medicine at UCLA has become the first scientist known to have used the new techniques of genetic engineering on human subjects. k
Dr. Martin J. Cline, a specialist in blood disorders, attempted to treat two patients suffering from a fatal blood disease by placing normal genes in their defective bone-marrow cells.
Cline performed the procedure in Italy and Israel at a time when he was awaiting permission to do it at UCLA. That permission was later denied until further work has been done with animals.
The results of the experiment are inconclusive, Cline told the Los Angeles Times, and they are unpublished.
Cline agreed to talk about the experiment because of the growing controversy that surrounds it.
The Office of Protection from Research Risks for the National Institutes of Health, the federal agency that funds the largest share of non-military scientific research, is investigating Cline's work.
At issue is whether Cline followed federal guidelines for protecting human subjects from possible harm.
Until recently, genetic engineering was confined to the test tube, and it was widely believed that applying the technology to alter the genes of animals was years away.
But events have moved ahead rapidly. Cline and others at UCLA reported the first succesful use of the new technology on the bone marrow of mice this spring, the first time genetic engineering had been applied to a whole animal. And, last month, researchers from Yale reported that they had succeeded in altering the genes of mice by treating fertilized eggs, apparently altering the makeup of every cell in the animals' bodies.
No one had taken the final leap of attempting an experiment in humans. But Cline proposed doing just that in the spring of 1979.
Scientists informed of the experiment had mixed views of Cline's decision to go ahead with a human subject. Many of those interviewed said they believe there are too many unanswered questions and that it is premature to proceed with experiments involving humans.
"I just think we ought to go a little more slowly," said Robert Schimke, a Stanford University biology professor.
A human subject protection committee at UCLA, after more than a year of deliberation, refused to grant Cline permission to do human experiments without further work on laboratory animals
Without that permission, under federal and university rules, Cline could not do the experiment on the UCLA campus. (The committee must determine whether the risks of a human experiment are balanced by expected benefits.)
Even before that decision was reached on July 22, however, Cline had performed the experiment on two young women -- one at Hadassah Hospital in Jerusalem, the other at University Poly Clinic in Naples.
Cline said in an interview that it was not his intention in leaving the country to evade the federal rules for human experiments. The Israeli hospital subjected the genetic experiment to the same scrutiny required by the federal guidelines, Cline said.
The Italian center used a more informal procedure, according to Cline, but still took steps to ensure that the patient was informed of risks and that the potential benefits outweighed any possible harm.
The first patient, a 21-year-old woman, was treated in Jerusalem on July 10 and 11. The second patient, a 16-year-old girl, was given the gene treatment on July 15 in Naples.
Both women suffer from a disease common among people native to countries of the Mediterranean -- betathalassemia major. Cline said he left this country to do the experiments only because it was easier to find thalassemia patients outside the United States.
Such patients lack the ability to produce normal amounts of hemoglobin, the molecule in red blood cells that carries oxygen to the tissues of the body. t
With continual blood transfusions, thalessemia patients sometimes live into adulthood, but the condition takes its toll on the ability of patients to live normally. Both patients treated by Cline had heart problems as a result of their transfusions, which cause iron to build up in the heart, leading to heartbeat irregularities and ultimately heart failure. Earlier this year, Cline and other colleagues at UCLA announced the first experiments in which new genetic material was successfully transferred to a living animal.
The experiments, in mice, indicated it might soon be possible to apply the same techinques to humans.
And that is what Cline and his colleagues in Israel and Italy attempted to do with the two thalassemia patients.
In both cases, the physicians removed a small amount of bone marrow from the patient and then exposed the cells to genes capable of producing the normal blood component the patient was lacking.
The marrow cells were then returned to the patient.
The hope was that the patients would begin producing normal hemoglobin.
After almost three months, there is yet to be any evidence of success or failure. Cline is still analyzing blood and marrow samples that have been taken regularly from the patients since their treatment.
It is possible that the experiment was a partial success -- that the normal genes were transferred but for some reason did not produce the normal hemoglobin or produced it in only small amounts. Cline said he believes it may take several three to six more months to find out.
Both patients are alive and doing well, according to Cline. Neither was bedridden at the time of the treatment, despite the seriousness of their conditions.
Cline agrees that placing genes in human cells is "uncharted ground" -- the reason he believes the UCLA committee refused to permit his proposed human experiments.
But he refers to animal results, some of them still unpublished, to prove that the worst possibilities are unlikely.
"It will take many, many years to understand all the controls on human genes in man," Cline said.
"When do you consider animal experiments adequate?" Cline asked. "When do you feel ready for a transition [to man]?
"Here's a patient who has a life-threatening disease with a limited life expectancy and no options with modern treatment. Is now the time to try an experimental treatment?"