Hunting for a Cure
Bethell, Tom
In the summer of 1977, Scott R. King had just graduated from the University of Chicago when he took a trip down the Mississippi Valley to visit a friend in Louisiana. On the journey south by car,...
...So he spent several months interviewing experts...
...The surface of the sheet had cracked, exposing the interior polyester mesh, which gives "tear strength" to the sheet...
...So he went to work as affects over ten times as many people as Type l.Type 2 is now said to be "epidemic...
...It could simply be osmotic pressure...
...My job is to work as hard as I can on what I am trying to do and to make our failures and our successes available to everybody, so that, if necessary, somebody else can take it all the way...
...Only in the last few years have researchers—Randy Dorian in particular—known how to do this...
...It came at a time of anxiety...
...He put this idea to good use in the 1990s while working on another product for Scott King, called PlasmaSeal...
...This leaves the vast majority of diabetics, including Scott King, out of the loop...
...The new prescription for his eyeglasses was already inadequate...
...Where the genetic basis is known, interest drops off because it turns out that no one can do anything with the information...
...At that moment I suddenly felt, 'Okay, this is all right.'What God was telling me was 'Don't worry about it, this is child's play for me...
...as it is" says David Geller of the University of Pittsburgh...
...With xenografts the immune response is fierce—there is at the moment no chance of success without suppressive drugs...
...But then he has a very personal interest...
...Still, immune-suppression comes with a high price...
...Allograft without immune suppression is the great current challenge...
...What we do know about juvenile diabetes is that it is an autoimmune disease...
...San Diego, worked as a researcher at the Salk Institute, and has wide experience in the biotech field...
...That is the body's third layer of defense against intruders...
...Researchers have tried to design alternatives not recognized by the body, but nobody has come up with anything as effective as alginate...
...It was a reasonable criticism because, to save wear and tear on the dog, Rilo had removed the pancreas and inserted the sheet in the same operation...
...On other sites, notably the liver, the sheets remained attached and undisturbed for many weeks...
...Nonetheless, it is easy to imagine a substance with pores that let grains of sand in, and peppercorns out, but exclude marbles and Cunard liners...
...Seemingly so straightforward, it has not yet been solved by anyone...
...The good news was that, when the sheet was removed, damaged though it was, the dog's blood sugar rose abruptly...
...They have portals which must be unlocked by a special device...
...Scott compares the measurement of blood sugar to flying blind in a fog...
...But it is not cosmetic surgery...
...Others think it will never work—that diseases—perhaps as many as 100, Dorian thinks—a new route to a cure would also be opened up...
...But equally great difficulties will lie ahead...
...Cards could be made large enough—the size of a notebook page—to contain a million islets...
...Whatever polymer or protective device is used," he said, "the immune system will probably react to that as well...
...It worked...
...At that point Scott King got back in touch with the Juvenile Diabetes Research Foundation and told them what had happened...
...This spring, they will return to Edmonton for further experiments using the liver and a few other sites that looked good...
...Metal plates fastening bones together will be walled up with these fibers, but that doesn't matter because there is no biochemical action across the plate...
...This was "Type 1," or juvenile diatransparent saline...
...On the journey south by car, Scott for the first time experienced the symptoms of diabetes...
...Once again, they found that sheets on the omentum became crumpled and soon attracted a fibrotic reaction...
...The pilot needs to know his altitude without delay...
...If something larger than a few cells from the outside is put in the body, the first line of bodily defense is to wall it off with a dense mesh of collagen fibers, whether the foreign object is alive or not...
...But the switch to human insulin did not noticeably affect the course of the disease...
...Nature made it," he said...
...So they are very sophisticated devices...
...But Scott King is an optimist, always has been...
...So it was the Islet Sheet that had cured it, and not residual islets...
...Bodies and organs are complex things made up of simpler parts...
...Although it has now come to an end, Johnson & Johnson's money freed the three to do the Islet Sheet research, on which to date Scott has spent about $550,000, without compensation...
...Randy finds this situation frustrating...
...That is brought on by low blood sugar...
...When I asked him one day about the source of his hope he said: "It has been a long slog, and there have been big disappointments and setbacks...
...Islet cells do sophisticated things, then, and contain machinery that is much more complex than mere "building blocks," and we don't know how they get the job done...
...It is the same with all other diseases whose genetic basis is known—sickle cell anemia, for example, or muscular dystrophy, or cystic fibrosis, or Huntington's chorea, or Tay-Sachs disease...
...Ultimately, when such questions arise in science, theory must defer to practice...
...Normal is 80...
...For that they won the Nobel Prize in 1923...
...For a while he also worked on Type 2 or "adult onset" diabetes, which covered the role of insulin in 1921...
...He made Scott an offer...
...So when you go back to investors now and say 'We are going to cure diabetes by transplanting islets in this marvelous capsule,' they say, 'Oh, we already invested in that...
...We don't even begin to know how to make these (or any other) cells with molecular parts...
...If people with non-severe diabetes—such as himself—are to be cured, they will have to get the islets from somewhere...
...The biological analogue is not likely to work any time soon—not, at least, until the molecular "building blocks" of the body, and their interactions, are much better understood than they are today...
...It is sobering to realize that, although diabetes is one of the most carefully studied and best understood of human diseases, and the big advance in understanding it was made 80 years ago by country doctors in Canada, we are still unable to cure it...
...Curing diabetes in rodents, frequently but superfluously demonstrated, is "trivial," Scott says...
...Half an hour later you start sweating...
...Adult onset diabetes has received a lot of attention lately, including a cover story in Newsweek...
...Talking about the machinery of islet cells one day, Scott said: "If you hook a glucose sensor up to a computer which in turn drives an insulin pump, in an attempt to simulate what a beta cell does, the control is nowhere near what an islet can achieve...
...This reminds us how great are the difficulties of biotechnology, and how far we still are from the "breakthroughs" that are daily touted in press releases, deplored by some, viewed with fashionable alarm by others, but rarely examined calmly and skeptically...
...That's all that PlasmaSeal does...
...A company in southern California called Neocrin "went through in excess of $80 million in an attempt to get pig islets into monkeys," King said...
...Some researchers have claimed that they can do this, but the problem is that after they have divided a few times in culture they lose their specific glucose-measuring, insulin-producing function...
...Transplants come in three broad varieties: autograft (organs are removed and later returned to the same animal), xenograft (from one species to another), and allograft (from one individual to another of the same species...
...Rick Storrs points out that the sugars that constitute alginate are not found in infectious organisms such as parasites and bacteria...
...It was all very sudden," Scott said...
...Somehow they seem to play a protective role...
...There has been much improvement in these drug regimes, with the removal of the steroids that were in particular believed to be harming the islet cells, and that was probably the key to Edmonton's success...
...Pigs and cows, of course, were the source of insulin in the past...
...Nowadays, diabetics take a drop of their own blood and put it on a small inexpensive meter at home...
...At least, they achieved it for twelve weeks...
...In the nearly 24 years since his diagnosis, therefore, Scott King has been highly focused on finding a cure...
...Our approach is holistic," Randy says...
...Within hours of injecting the islets, all their patients were off insulin...
...By then it might be too late...
...For the cost of a house in Silicon Valley we think we can prove we have the cure for diabetes...
...It shows that the coverage of the islets is complete," said Dorian...
...Approved by the FDA in 1982, it was the first product of genetic engineering to be accepted for human use by the U.S...
...Jonathan Lakey and James Shapiro...
...For organ transplants of all types, over 72,000 patients are waiting...
...Fashion rules, in science as in so many areas of life...
...These tests have compared different sites in the dog, to discern which ones are hospitable to the sheets...
...Too many researchers in this field have focused on one design issue and ignored essential others...
...He has a bachelors degree in biochemistry from U.C...
...Alginate has been used in the food processing industry for decades, and has found medical applications within the last 20 years...
...It naturally has the physical qualities that are needed to render it, and its contents, invisible to the body...
...This is a "hemostatic" agent, meaning that it stops bleeding quickly...
...The cliche about human flesh being "heir to" disease is true in the case of diabetes...
...They measure many things in the blood, of which glucose is only the most important...
...His blood sugar turned out to be about 600 milligrams per deciliter—almost off the scale...
...Today he has his own biotech, Islet Sheet Medical, located in the industrial flats in the south-east part of the city...
...When you promise a cure and don't deliver, people remember...
...Banting and Best demonstrated the action of insulin in dogs...
...Scott King believes that that will take at least another 50 years.That would be too late for him, and for most of us...
...Man had to mix his labor with it—by refining it to rid it of all impurities, specifically proteins...
...The unsolved problem is this: to transplant a functioning organ from one body to another—and an islet is an "organ," an organized cluster of cells—and retain that function in the recipient without suppressing the immune system...
...A simpler system might be one in which your blood sugar goes up when you eat a meal, and then comes down as it is used up...
...But I do believe that God is going to cure diabetes and that I think I have a role in that...
...In the late 1970s, human insulin was engineered by recom-binant DNA technology...
...Thirst signals are sent to the brain, and the ensuing drinking and urinating eliminate some of the excess glucose, but it builds up again...
...Once they find out that the islets don't know the "password," the islets will not have long to live...
...In pure form it is a liquid, which turns into rubbery gel when calcium is added...
...Rilo, who had trained for seven years at the Starzl Institute at Pittsburgh, and who moved to the University of Cincinnati in 1999...
...You can do it, too.'" 66 THE AMERICAN SPECTATOR ¦ March 2001...
...You can do it, too.'" 66 THE AMERICAN SPECTATOR ¦ March 2001's play for me...
...It exposes patients to infections, and can cause lymphoma, or cancer of the white blood cells...
...Individuals with certain alleles, or varieties, of three genes in particular have a very low chance of getting diabetes...
...After a month, Scott King contacted the Juvenile Diabetes Research Foundation in New York...
...Only half of one percent of the U.S...
...So we thought it would be simpler just to remove water from the blood, rather than try to purify a single component...
...Several years ago, Randy Dorian developed a way of encasing islets indi62 THE AMERICAN SPECTATOR ¦ March 2001 vidually in a protective cocoon, thereby concealing them at least some of the time...
...Because the animal islets are immediately available, however, success with xenografts would mean that a cure for Type 1 diabetes would be at hand, and that a new treatment might be available for a wide range of other diseases as well...
...He wasn't feeling right at all...
...Twice daily, the blood sugar of the animal was tested, and almost immediately was shown to be normal...
...This is an organization that spends $100 million a year on diabetes research and is dedicated to finding a cure...
...Gene research nonetheless gobbles up tens of millions a year in diabetes research-dollars, and may be expected to continue doing so...
...One remaining solution is to transplant the islets from one body to another...
...The bio-invisibility of alginate, much discussed at a recent conference in Davos, has been confirmed by Gordon Weir's group at the Joslin Clinic at Harvard...
...The smoothness of the surface also seems to be important...
...Over time that destroys tissues that are particularly dependent on the capillaries, like the kidney, the retina, the peripheral areas...
...We are optimistic because we know we have not ignored any of the requirements for success...
...The insulin is already bringing it down...
...So the transplant procedure is confined to those with severe diabetes, particularly a condition called "hypoglycemia unawareness...
...Implanted cells in sheets could produce many of the new 'wonder drugs' promised by biotechnology but which are difficult to administer," says Rick Storrs...
...It removed a lot of proteins normally present in clots, substances that are not even known, and was moving Alginate naturally has the physical qualities needed to render it, and its contents, invisible to the body...
...Islets actually anticipate changes...
...In February 2000, the pancreas was removed from a dog, and in the same procedure sheets loaded with islets from another dog were implanted...
...Refined algi-nate is that substance...
...For dogs, Randy and Rick have been making sheets about the size of a business card, and two cards of that size are needed to cure a dog...
...w hen I came down with diabetes the standard home therapy was to measure the sugar in your urine," Scott said...
...He had the interest, but not the temperament...
...Well," the doctor in Lake Charles told him, "I'll take your blood sugar just to be sure, but you've got diabetes...
...A monthly doctor's visit is like having to throw a plumb line out of the plane and wait until it hits the ground...
...New organs brought in from foreign donors would inevitably set off the alarm bells of the immune system—particularly as the immune systems of diabetics already have their knives out for islet cells...
...If success does come his way, that undoubtedly will have been his secret weapon...
...His eyesight was also changing—rapidly...
...But after organizational and financial struggles that are par for the biotech course, the patents are now owned by the University of California...
...Current theory strives to implicate viruses, but that fashion, too, will no doubt pass...
...The disease came on in about two weeks...
...population contracts the disease, but the identical twin of a juvenile diabetic has a one-in-three chance...
...in New York...
...Oxygen is delivered by red blood cells, in packets of hemoglobin...
...The scientist who most inspired Randy was a cancer expert named Dr...
...If they make contact with a foreign cell, they launch peroxide bombs and kill it...
...With the impurities, the alginate will attract an immune reaction within days...
...They are hooked up to the nervous system.You intend to eat, let's say, but then the phone rings and so you don't...
...Yet this knowledge has had absolutely no therapeutic consequences," Scott says...
...At the moment, the fashionable thing is to "reduce biology to physics," as Scott King puts it...
...It can cause problems worse than the original disease...
...It is as though the constant up and down, up and down, not noticed much at first, eventually makes everyone in the plane thoroughly sick...
...Scott will be able to claim a great victory...
...So we have to ensure that not a single islet is exposed on the surface of the sheet, because if the T-cells find one cell they will get the one next to it, and soon the entire islet," Scott said...
...In this way, cells are "vascularized...
...That is what Scott and his colleagues Randy Dorian and Rick Storrs at Islet Sheet Medical have been working on over the last few years...
...There is so . much motion that the sheet had not stayed firmly attached, but had twisted and rolled...
...By the 1930s, insulin extracted from pigs or cows had become commercially available, and after that the disease was no longer a death sentence...
...Sometimes he will work at the bench all night and have a functioning device by morning...
...Randy Dorian developed the scientific investigations, that simpler is better, and that in biology simplicity is often better achieved by subtraction than by addition...
...So it is "genetic," but no one really knows what that means...
...At the moment, the investment climate in islet transplantation is not good because millions in venture capital were spent and lost in the search over the past fifteen years...
...To claim a cure without immune suppression, Scott King says, they will THE AMERICAN SPECTATOR ¦ March 2001 65 have to demonstrate it for at least nine months...
...In a matter of weeks the untreated patient will die...
...It involves elevated blood sugar, but it is treatable by improved diet and exercise, and it is so different from juvenile diabetes that arguably the two forms should be given different names...
...They can get the result in a minute or less...
...Details are always important, but many researchers become so obsessed with a molecule that they lose sight of the organism...
...Nothing else has...
...There, he absorbed the important lesson that he brings to all his toward an artificial clot, quite different from what nature intended...
...Berkeley, and his expertise in pharmaceutical development, Rick Storrs confers formal respectability on the trio as Chief Actuator...
...Diabetics who take insulin injections develop medical problems over time because they do not have a way of delivering the right amount of insulin, at the right moment, to the bloodstream...
...Investors lost...
...Rose asked him to help out in his lab at Salk, which Randy did for a couple of years...
...Insulin injections leave them with blood sugar so low that they can go into a coma, but they feel okay until it's too late...
...The company was reorganized as Novocell, employing one-tenth the number of workers...
...Scott King believes that, in the course of two years, he ages three...
...Nature made it It works...
...We have a 120-year history of studying diabetes in dogs," Scott said...
...Alginate works...
...It occurred to us that this was the complicated way...
...To revert to the airplane metaphor, assume the plane on its journey is supposed to be flying at a constant altitude...
...Therefore, cells in the sheet must remain close to live tissue, like prisoners in a crowded boxcar who must stay on the outside to avoid suffoca-tion.That in turn means the sheet must be thin—not more than one-third of a millimeter, equivalent to a contact lens...
...But we won't know until we try it...
...Throughout it all, Scott King remains cheerful and ebullient and, above all, filled with optimism...
...So the big opportunity and unanswered question that confronts Islet Sheet Medical is whether their method will work with xenografts—from one animal to another...
...It's worth pausing to describe the problem that the Islet Sheet must solve...
...At least once a day, if you spend time with Scott King, he will tell you that there are much easier ways of making money...
...And we can't grow them in cell lines...
...There are a million islets in humans, maybe 250 to 1,000 cells to an islet...
...It thinks of itself as starving...
...The body's own immune system makes a systematic mistake, and attacks the "beta" cells of the pancreas that produce insulin...
...Euglycemia" (good blood sugar) lasted for 84 days, but by then signs of trouble were beginning to appear and they opened up the dog...
...Citric acid turns the gel back into a liquid again...
...The islet cells must never be too far away from living tissue because the oxygen must "diffuse" in, which in practice means that it must not have far to travel or it will become too attenuated...
...He did his work well enough that he was allowed to write a report on the work in progress in diabetes...
...Others think it will take 100 years...
...If blood sugar varies a lot, as mine does, it breaks down blood vessels all over the body...
...But there is an additional difficulty...
...It must let nutrients in, and it must let the insulin out...
...It must not provoke a fibrotic reaction, nor let the T-cells touch the islets...
...He was "sort of meditating," when, in the vision, a child-like figure was playing with a bunch of Islets of Langerhans, throwing them in the air with delight, as children do...
...Without it, the glucose stays in the bloodstream, building up...
...If the sheet develops thin cracks, Scott noticed, lines of fibroblasts appear in the cracks...
...When the concentration of something increases, membranes swell...
...But they wanted to continue their collaboration with Dr...
...With or without xenografts, Islet Sheet Medical will find it easier to raise money if they can claim a cure without immune suppression...
...One says that if you isolate the islets and deny access to the T-cells, that will be sufficient to protect the islets...
...They become "de-differentiated," in the jargon of cell biology...
...And the probable end is not reassuring...
...Had they waited for an interval before inserting the sheet, they could have demonstrated that the dog was diabetic...
...One surgeon has compared the operation to "peeling steel off wallpaper...
...Their metabolism is quite unlike that of humans...
...to date have not even been able to keep out the Queen Mary...
...He monitors his blood sugar constantly, and must treat the disease with self-administered insulin injections, four or more times a day...
...No longer do diabetics have to go to a doctor's office, where a computer the size of an oven would be used to measure the glucose in a vial of blood...
...Meanwhile, the company will be able to keep going with support from individuals and friends...
...The reason is that their membranes or coatings have defects—they do not completely cover all the islets...
...And the exposed polyester, recognized as foreign, was beginning to attract a fibrotic response...
...When Islet Sheets were described to transplant surgeon David Geller of the University of Pittsburgh's Thomas E. Starzl Transplantation Institute, perhaps the leading such center in the world, he said he wasn't familiar with the technology, but he assumed that it would encounter the familiar problems...
...Then with a grin he threw them at me and laughed...
...Johnson & Johnson took a license to the technology and spent about three years in development...
...Before the medical application of insulin, diabetes was fatal...
...Their normal blood-sugar concentration is the same as humans, and their insulin, although differing in only one amino acid in the case of the pig, doesn't cause problems in humans...
...In 1983 Scott moved to San Francisco, where he began to analyze the financial prospects of the biotech industry, then blossoming in the Bay Area...
...Islet cells, in contrast, deliver insulin with such smooth precision that the level stays even and passengers don't feel a thing...
...If normal blood sugar is 80, and it rises to 100 before insulin is injected, and then falls back to 60, the "average" 60 THE AMERICAN SPECTATOR ¦ March 2001 may be 80 but the harm to the blood vessels—the vasculature—comes from the range of departure from normal...
...government.There followed a period of great expectations, because the pig insulin that had been widely used differs from the human variety in one amino acid...
...With his Ph.D...
...The dollar cost is quite high— about $25,000 per transplant experiment...
...Since then, Islet Sheet Medical has done a further round of experiments at the University of Alberta, in collaboration with Drs...
...The elaborate mechanism to keep blood sugar constant tells us that there is a good reason for doing so," Scott added...
...One who read his report, "The Future of the Diabetes Industry," was the head of Montgomery Securities in San Francisco, whose daughter had just been diagnosed with the disease...
...A measure within a minute, on the other hand, is a pretty good altimeter...
...Sam Rose, an independent-minded researcher who was at the Salk Institute for years.They met when Randy was still in high school, demonstrating a project at a science fair...
...Despite that," Randy Dorian said, "almost all of the researchers in this field Gene research gobbles up tens of millions a year in diabetes dollars, and has had no impact on treatment...
...We just accept what is," said Randy...
...The genes "associated with" juvenile diabetes are known, and have been known for a decade...
...At the moment, organ donors are the only source, and there are barely enough of these to cope with the demand for those with the acute form of the disease...
...Autograft is trivial—there is no immune response...
...The demand for islets far outstrips the supply mystical immunological phenomena will kick in and destroy a cell type that is so different from that of the host...
...If part of the original pancreas remained—and it is not easy to remove it all—then the original islet cells, not the transplanted ones, could be stabilizing the blood sugar...
...Gregory of Nyssa Episcopal Church in San Francisco, and writes music for their services...
...We're happy/' philosophy and invented the methods behind the Islet Sheet that the company is now testing...
...Starved of nutrients, they will die...
...That is the all-important variable...
...Worse, T-cells will go off and "inform" on the invaders, sensitizing the B-cells to make antibodies to this particular type of invader...
...But one big problem remained...
...Islets within the smooth sheet appear as bumps in the electron micrograph at left...
...But the lesson Randy learned from Sam Rose—take nature whole and remove elements if necessary, don't try to reproduce it from the bottom up—has also begun to yield results in Islet Sheet Medical...
...Cells deprived of oxygen send out distress signals, causing capillaries to "reach out" to them...
...Scott's work on that ill-defined disease is now on hold, and has been for several years...
...Islet Sheet Medical has far to go, with human trials still to come if the sheet proves itself in dogs...
...More recently he came up with something better: a thin polymer sheet, into which living islets can be placed...
...Even with insulin those with juvenile diabetes rarely live to an old age, so the disease tends to concentrate their minds...
...But this cannot be allowed to happen within the sheet, because along with the oxygen-bearing blood cells will come the killer T-cells...
...Macrophages and T-cells are the next layer of immune defense...
...It is not only elevated blood sugar that damages tissue...
...If a molecule of oxygen is compared to a mustard seed, glucose is the size of an ordinary grain of sand, insulin the size of a peppercorn, an antibody is a marble, and a T-cell is...the Queen Mary...
...In their micro-encapsulation system, islets were immersed in chemicals and zapped with laser light...
...The genetic defects causing these diseases were known long before last summer's self-congratulatory celebration of the human genome project...
...Might it be possible, then, to arrange a "stealth" transplant of islets, without alerting the immune system...
...His own, far more serious condition is more urgent...
...Within weeks the fibrous prison would have thoroughly sealed off and starved the islets within...
...There's an awkward if rarely stated rule of thumb: Genetic analysis is only interesting in those diseases where the role of genes is not known (cancer research, for example, has been a hotbed of gene-enthusiasm for 20 years...
...Before the discovery of insulin it was quickly fatal...
...Fortunately, nature has arranged things in such a way that it is possible to admit essential supplies while excluding the enemy...
...The Canadian scientists Charles Best (who had not yet entered medical school) and Frederick Banting and two others at the University of Toronto, disBY TOM BETHELL Americans suffer from it, and the inci-dence is increasing...
...But knowing the genes has had no impact on treatment...
...Why the immune system behaves properly with most people, but occasionally launches this inappropriate attack on a vital organ in others, is one of the greatest unsolved mysteries of diabetes...
...The protective alginate sheet therefore must meet tough requirements...
...There are two camps...
...The Juvenile Diabetes Research Foundation estimates that sufferers lose 15 years of life on average...
...Building blocks"—that is the favorite metaphor of molecular biology...
...Jeremy Knowles...
...We're happy...
...Horacio Rilo's transplant team there, they encountered problems both with the structural integrity of the sheet and with the cell-culture medium that was "feeding" the islets as they awaited implantation...
...The sheets had been attached to a flexible flap of tissue in the front of the stomach called the omentum, this being an easy place for a surgeon to reach...
...It was there, last year, that Islet Sheet Medical achieved what they had been trying to do...
...The immune system that had killed off the original islet cells would still be in place...
...But it wasn't a total gift...
...You've got all the symptoms...
...Organ donors provide about six thousand pancreases a year...
...But the body's cells are not just open doors into which the glucose can flow at will...
...He has not heard back from them yet...
...Obviously you didn't make the dog diabetic in the first place," King was told...
...Over the years, the oscillation up and down breaks down small blood vessels in particular, and that is why limbs cease to heal properly, and eyes and kidneys fail...
...He lives half the time in San Diego with his wife and seven monkeys (two guenons, two white-faced capuchins, two squirrel monkeys, and one spider monkey) and then clambers aboard his Jeep and drives north, spending days at a time in the San Francisco lab...
...It is as though a tribe of builders, having learned how to make bricks, and observing from a distance that factories are made of bricks, at least externally, decide that they can, by an appropriate assembly of bricks, re-create the goods manufactured inside the factories...
...That key is insulin...
...They have gaping holes in their coverage" through which whole immune-system flotillas can pass...
...What makes it invisible to the body...
...So blood-sugar monitoring at home is by far the most important development in my lifetime, because it allows patients to exercise much better control over their blood sugar...
...The chemistry seemed to be "very elegant," Scott said, but it "just doesn't seem to be good for the islets...
...He developed a thirst that wouldn't quit, and he was visiting the urinals as often as the drinking fountains...
...And they do seem to be close to that For a number of other The problem Islet Sheet must solve reminds us how far we are from the biotechnology "breakthroughs" touted in press releases and viewed with fashionable alarm...
...So what any good researcher must do, to attract the admiration of his peers and the big government grants, is take those simpler parts—the nucleotide sequence of the genome in particular (now "decoded," they say, but by that they mean encoded)—and try to build them up into those complex wholes...
...And you don't get sugar in your urine unless your blood sugar is very high...
...First the pancreas must be removed to make the dog diabetic, then the foreign islets are inserted, and then the blood sugar is observed over the next six months...
...THE AMERICAN SPECTATOR ¦ March 2001 59 Since then, the most important innovation, and it is an important one, has been the introduction of home glucose testing...
...These pancreatic cells come in clusters which, when first detected under the microscope by the German histologist Paul Langerhans, resembled the islets of an archipelago...
...I was depressed and unhappy and thought that we had foundered," he said...
...When food is digested, carbohydrates and most proteins are converted into glucose, and this must be delivered to the body's cells, particularly muscle cells, as fuel...
...But after a year he found that graduate school was not for him...
...If you know you are going to eat a meal, for example, islets will start making insulin before you have eaten...
...A few years ago he had a "vision...
...It works...
...People often try to address a problem by increasing its complexity," Randy said...
...The polymer is alginate derived from kelp, or seaweed, and he thinks of it as one of nature's gifts to man...
...Ultimately, however, empiricism rules...
...With hemostatic agents, for example, "most people were precipitating fibrino-gen, which is the main component of a blood clot, in order to increase its concentration...
...Mary Tyler Moore, the best known "poster person" for Type 1 diabetes, recently had the increasingly cloudy vitreous humor of her eyeballs removed and replaced by After he was diagnosed with diabetes, & Co...
...In her case, the vitrec-tomy, as it is called, was successful...
...In desperation, new signals are sent out to devour the muscles themselves and convert them into glucose, and so the body consumes itself...
...Without the insulin key to admit the glucose to muscle and brain cells, however, the body is in a very bad way...
...So what will happen if they put pig islets, protected by the sheet, in humans without suppressing the immune system...
...It is an attractive vision...
...Therefore islet transplants require anti-rejection drugs to suppress the immune system...
...w We do think ti"s to work," Randy said one day in the lab, surrounded by his microscopes, autoclaves, centrifuges and a bio-containment hood to ward off contamination...
...But if foreign, living tissue—a fluke in the liver, for example—is encased in this fibrous shell, it will soon die...
...He is a cantor at St...
...In preliminary experiments at the University of Chicago in 1998, with Dr...
...in biophysical chemistry from U.C...
...The Juvenile Diabetes Research Foundation called it a "significant step forward," and President Clinton announced an NIH-funded study to replicate the technique at ten hospitals...
...Blindness is common, the kidneys fail, limbs sometimes have to be amputated...
...If you can cure diabetes in a dog, you can do so in a human...
...Oxygen is the most urgently needed nutrient, glucose is another...
...So here is the problem: Foreign islet cells will get the same unfriendly reception as a liver fluke...
...Consequently they are known as the Islets of Langerhans...
...For 20 years or more, medical centers tried transplanting them into human patients who were severely ill with diabetes.Then, last summer, researchers at the University of Edmonton in Alberta succeeded...
...So the way we prevent the antibody reaction is to make sure the T-cells never have access to our islets in the first place," Scott said...
...This is what the Islet Sheet is made of, the gelled form of alginate...
...The efficacy of the device would have to be demonstrated in dogs first...
...They found, however, that it is not a good site...
...No one has been able to do anything with the information...
...It is treatable by the daily injection of the hormone insulin, but it is not curable...
...If an immunological response has not occurred by then, and good blood sugar is measured throughout, the Islet Sheet will have proved itself...
...Once it is imprisoned, nutrients will be prevented from entering and, if it is alive, it will then die...
...The results were not satisfactory...
...The membranes around my capillaries are unusually thick, as they are with all diabetics...
...So we did...
...Two months after his diagnosis, Scott King began graduate work in biochemistry at Harvard, studying enzymes in the lab of Prof...
...He was 22 years old...
...Scott, who switched from pig to the genetically engineered variety in the 1980s, says that the main effect was to double the price...
...It doesn't work.' And saying 'we are smarter than them' somehow isn't a strong selling point...
...Randy is a "genius," Scott thinks...
...In the last year, he believes, he and his two co-workers at a small biotechnology firm in San Francisco have made an important breakthrough—one that could cure not just juvenile diabetes but other diseases as well...
...It has the curious property of being a reversible gel...
...It is very useful in surgery...
...In the same way, the fibrotic response to a dacron graft in a THE AMERICAN SPECTATOR ¦ March 2001 63 burst artery will only aid the desired result of channeling arterial blood...
Vol. 34 • March 2001 • No. 2
