In a success that heralds a major new medical technology, researchers have created a "living pill" that administers insulin in a slow steady flow to diabetic laboratory animals. The technique, in which capsules full of live, drug-producing cells are injected into the body, holds out the promise of vastly improved treatment for hormonal or enzyme deficiencies and posibily even of artificial organs made of thousands of the tiny pills.
The technology may also provide a new way of delivering ordinary drugs to the body over long periods of time; it may create a new way of storing live cells, such as red blood, or other delicate biological commodities many times longer than is now possible, and it may become a powerful new research tool as well.
The recent experiment by Franklin Lim, of the Medical College of Virginia, and Anthony Sun, of the Connaught Research Institute in Ontario, represents the first time live cells have been successfully enclosed in capsules for a long period.
The living pill in the recent experiments is a special porous membrane woven of long molecules around a core of live, insulin-producing pancreatic cells. The encapsulted cells were implanted in the chests of diabetic rats and succeeded in curing the effects of their diabetes for the three weeks the pills were in place.
The success with diabetic rats was suggested by Lim and Sum in Science magazine recently as a novel and potentially useful method of evading the body's powerful immune system which would normally reject and then kill any intruding foreign cells.
The implanted cells are protected by the microcapsule: the membrane of the capsule allows nutrients in, and insulin molecules out, because they are small enough to penetrate the tiny gaps in the membrane. Attacks by the large cells of the body's immune system are prevented because the attacking cells are too large to penetrate the membrane.
In the same experiment, other pancreatic cells were implanted in the rats, but without the special membrane capsule. They were routed by the body in about six days.
About 3,000 of the pinpoint-sized capsules were injected into the test animals, said Lim. For 20 days the encapsulated cells lived inside the rats' bodies and eliminated the effects of diabetes, until finally body tissues possibly began tp clog the pores of the capsules, or possibly the capsules eventually broke down under the attack of the immune system, since the capsules were a first-generation batch.
Researchers are now trying to extend the useful lifetime of the capsules less irritating to body tissues, Lim said, and possibly by picking other sites for implantation. They speculate that they may be able to get between three and six months life from capsules eventually, a potential boon to diabetics who now must take injections of insulin daily.
In the past, microcapsules have been used outside the body in filtering systems that remove toxins from the blood by passing it through a bed of microcapsules filled with charcoal or some other filter material. The red cells are too large to enter the capsules, but the toxins in the blood have molecules small enough to pass into capsules and be caught by the filter material, said Thomas Chang of McGill University, a pioneer in microencapsulation.
In a similar way, Chang said, packs of microcapsules holding live organ cells might act as artificial organs outside the body -- organs divided into thousands of little protective capsules -- which might be used just as kidney dialysis machines now can be used to periodically clean the body fluids. Work has already begun on the bioartificial liver and pancreas.
One of the expected uses of the microcapsules is to correct diseases which result from enzyme or hormone deficiencies. Live cells of the organ that produces each needed chemical could be encapsulated and implanted. For example, catalase is an enzyme which can break down hydrogen peroxide into water and oxygen; without it, the poisonous chemical can reach deadly levels in the system. Cells which make catalase have been grown experimentally in capsules.
One great advantage of using microcapsules is that animal cells can be used to produce needed chemicals, rather than relying on human cells harvested from cadavers, a process difficult enough to have created a shortage of many enzymes and hormones.
The chief barrier to implantation of microcapsules now is the question of what will happen to the tiny capsules in the body when injected. It is not known whether they will be safely eliminated, dissolved, or whether they may eventually become the center of cystlike growths.
Meanwhile, microencapsulateion is becoming a powerful research tool. One use, for example, may be to purify important biological chemicals, such as the antiviral agent interferon. If the cells that make interferon are placed in capsules, the tiny inteferon molecules can easily escape, while the bigger protein molecules which often contaminate samples of interferon would be trapped.
The traditional method of growing cells in the laboratory creates single layers of cells in the bottom of glass containers. For any large-scale work this takes up a great deal of space. Using microcapsules, the same nunmber of cells can be grown in clumps and the capsules themselves stacked in flasks, so that up to a hundred times as many cells can be grown in the same lab space. This makes mass production of interferon or other needed active biochemicals quicker and easier.
The size and the porosity of the capsules can be varied according to the job they have to do. In addition, the membranes can be made to be relatively permanent or to dissolve after differing amounts of time in the body.
The new method of making microcapsules, invented by Lim to protect living cells while encapsulating them, is relatively simple and fast. Whatever cell or drug is wanted in the capsule is first put in a heavy, almost gelatinous liquid. The cells and the liquid are then forced through a tiny tube, forming droplets as they come out into a thinner liquid. Added to this thin liquid are long-chain molecules, which gradually gravitate to the cell-containing droplets, and cling to their surfaces.
Gradually, layers of these long molecules form into something like an irregular weave around the droplet. A different sort of chain molecules may be added to give the ball a tougher skin.
The final step is to add a chemical that melts the gelatinous liquid so it can seep out of the capsule, leaving the cells encased as if in a cocoon.
This process produces a membrane that has enough gaps in the weave that molecules of a certain size can wiggle through while larger structures cannot.
The technology of miocroencapsulation, with the advances of Lim and Sun, "could be as important in a practical way as recombinant DNA research has been in basic research," Lim said. "Every scientist I talk to thinks up a new use for his field of this technology." What is needed now is time for the dozens of uses to be explored and applied in areas thorughout medicine and biology.