Biologists thought the first one of them to use genetic engineering in people rather than mice would be an instant candidate for the Nobel Prize. They were wrong.

The event has happened, and the reaction among leading scientists has been strongly critical. The experiment has been called a "tissue of crap" and "totally irresponsible."

Across the country, scientists are challenging the work by Dr. Martin J. Cline as unethical because it exposed human patients to unnecessary risk, and scientifically unsound because there is little reason to believe the experiments have any chance of succeeding.

"This is not just a little disagreement among colleagues," said expert in the field who is familiar with Cline and his work.

"You know we are almost never inclined to talk about colleagues like this," he said. "It is really very sad. But this stuff is too much -- it's such a tissue of crap and it makes us all look like horses asses. I do not understand why Cline would do this . . . "

The experiments were acknowledged last week by Cline. He performed them in July on two young women, 16 and 21, who have a fatal gentic disease of the bone marrow that prevents their bodies from making normal red blood cells.

Cline withdrew cells from the women's bone marrow, implanted fresh genes in them and returned them to the patients' bones. His hope is that the cells with fresh genes will multiply and make the red blood cells that the women's cells, with their defective genes, cannot.

Under conventional treatment, the women would be able to survive for a period of time through repeated blood transfusions but would face certain death because the side effects of the transfusions finally will cause heart failure.

The Washington Post Contacted more than a dozen scientists who are reputed to be the most knowledgeable in the field. Without exception, they expressed doubt and concern about the experiments. At best, they say, the experiment was risky and premature. It may be a decade before scientists have the knowledge necessary to carry it out properly and with a hope of success, they said.

Cline's experiments took place in hospitals in Italy and Israel. A UCLA committee on human experimentation refuse to allow him to conduct such work at that university. In the aftermath, the National Institutes of Health, which has funded Cline's research in the past, begun an investigation of the experiments to determine whether he followed federal guidelines on the protection of human subjects in experiments.

Dr. Kenneth Boyer of Johns Hopkins said that with genetic engineering in the public eye, scientists are particularly sensitive, "and none of us wanted this sort of thing to happen. It gives us all a black eye."

Though Cline now refuses to speak to reporters, last week he told The Post that "what is premature and what is not is a matter of judgment," and that history often has shown that those who went in early with a new, untested treatment were right to do so.

One of the bluntest of Cline's critics, reputedly one of the most knowledgeable researchers in the field of anemia and molecular genetics, put it this way:

"This work is totally and absolutely unacceptable. This is not science. There are some things in science which cannot be done. I think this is one of them. I don't think Cline has fabricated data, but I do challenge his judgment. He has no good data which give him any reason to carry this work to human beings. If it is true that he can do this, why didn't he do it first in animals and show that it can be done? The reason is because he can't do it.

"If he could do it in animals, let alone humans, that would be incredible. That would be good enough to go to Stockholm" for the Nobel Prize.

The objections from the scientists are twofold. First, that patients were subjected to an experiment with some risk and no hope of success, as they see it. Second, that Cline's animal work, in which he went through a similar process with mice and which was the backup for the human experiments, was inconclusive on most important points, but clearly did not show any hemoglobin being produced. The patients in Cline's human experiments cannot be helped if no hemoglobin is produced by the new genes he gave them.

Dr. David Nathan of the Children's Hospital in Boston, an expert on the type of work Cline is doing, said he feels that work with people "should only be done if the animal studies beforehand are very promising."

To understand the reason Nathan and others question the basis of the experiment, the sequence of steps in the experiment must be clear.

First, a needle was inserted repeatedly into the hip bone to suck out about a billion bone marrow cells. These cells, which had defective hemoglobin genes, were then mixed in a flask with little strings of healthy, prepared hemoglobin genes.

By some process still not understood, a small number of the fresh genes are likely to take up a place in the long strands of DNA within the cell.

Cline then took the mixed cells and genes and injected them back into the body. About 10 percent of this mixture should normally find its way back to the bone marrow, where possibly 100 to 1,000 cells, with fresh working genes, might begin to grow alongside the billions of other thriving but defective marrow cells.

Cline hopes that the cells will not only grow, but will reproduce so effectively as to crowd out many or all of the billions of other cells and thus revive the marrow. He says it will be several months before he has any results worth mentioning. After three months, the condition of the patients has showed no change.

In animal work so far, animals' bone marrow cells have had to be killed or be nonfunctioning before the few, newly injected cells will grow and take over the marrow. The common method of doing this is to give a dose of radiation to the animal's marrow and then introduce the new cells.

Another way of giving the newly injected cells a chance of competing with the billions of cells already there is to make the fresh cells resistant to a drug -- usually a toxic anticancer drug called methotrexate. The fresh, resistant cells will survive a dose of the drug, while the nonresistant cells in the marrow will give way.

But, according to Cline, no methotrexate was given and no marrow was irradiated in his human experiments.

"You have to realize," said one critical scientist, "that you are talking about 10 cells, I doubt if it's a hundred, finding their way to the bone marrow where there are 10 billion cells all growing like sixty and competing for space. Why should Cline's 10 cells [without the help of methotrexate or irradiation] be favored enough to take over? How could they push aside and dominate 10 billion other cells? There is no reason."

Sheldon Bernstein of the Jackson Laboratory, a specialist in mouse hematology, said that in several experiments marrow cells have been injected into mice without irradiation or drugs. The new cells do not populate the marrow.

And even beyond the question of whether the bone marrow cells will live and reproduce in the body, there is so far no evidence even from animal studies that shows that transplanted hemoglobin genes will go work and produce normal red blood cells.

Arthur Neinhuis of the NIH, another of the most knowledgeable scientists in the country on the subject, said Cline's experiment from what he could tell "has a very low, extremely low probability of succeeding. I would have to ask him why he did the experiment at all."

Thomas Maniatis, a molecular biologist at Caltech and one of the first scientists to work on the problem of hemoglobin gene production, commented on Cline's leap from animal experiments to human subjects:

"Clearly, [the animal experiments indicate] he hardly understands what is happening at the level of cells in culture, or at the level of the mouse. So to take such an experiment and do it on a person is totally irresponsible. It is incredible that he would do such a thing."

Maniatis went on the point out that scientists know so little about what occurs when genes are introduced artificially into systems that the risks of such an action can't even be assessed.

"You could try to make a list of things that could go wrong," he said. "There are some you might imagine in which the person would turn out worse after treatment than before," such as poor control of where the genes are placed, resulting in a worsening of the patient's anemia. Also, cancer could not be ruled out.

Cline's collaborator on the experiment, UCLA biochemist Winston Salser, explained that achieving hemologlobin production was not the most important aspect of the experiment as far as he was concerned, even though that is the critical factor in helping the patients. wSalser said he wanted to demonstrate that the gene could be inserted successfully in humans, especially without the use drugs such as methotrexate.

"It is going to be a long time before this disease is beaten. And you don't climb a building at a single bound. It's one step at a time. If it's only a question of getting massive [hemo] globin synthesis, if people are saying that, then I don't think that's the right call," Salser said.