Document BRY9ozNvYbXZ5eqJeQZvDo21j

HISTORICAL PERSPECTIVE ON INTER-INDUSTRY VINYL CHLORIDE STUDY 1960-1963 Report published documenting anesthetic effects in animals and humans and liver injury in animals from chronic exposure. 1967 Acroosteolysis reported in humans exposed to high levels of VCM. 1971 1973 Carcinogenicity of VCM discovered in animals, including angiosarcoma of the liver. CMA sponsors Tabershaw-Cooper Associates to conduct an epidemiologic study of 8,384 vinyl chloride workers from 34 plants. 1974 First reports of angiosarcoma of the liver cases in VCM workers. 1974 Tabershaw-Cooper report preliminary results confirming high risk of angiosarcoma of the liver and suggesting excess cancers of respiratory system, brain and lymphoma. GGB 3/15/94 SL 107236 HISTORICAL PERSPECTIVE ON INTER-INDUSTRY VINYL CHLORIDE STUDY (cont.) 1974 OSHA holds hearings and revises PEL down to 1 ppm. 1981 Cooper expands original epidemiology study to include 10,173 workers from 37 plants-- reports show angiosarcoma and brain cancer to be in excess through 1972. 1986 EHA updates inter-industiy study with follow-up through 1982reports angiosarcoma, brain cancer and emphysema to be in excess--no excess respiratory cancer or lymphoma/leukemia. 1991 EHA study is published. 1993 CMA letter to the editor and EHA response are published clarifying the brain cancer and emphysema findings. 1994 GGB 3/15/94 CMA Vinyl Chloride Research Coordinators meet to discuss updating study. SL 107237 "The study carried out by Environmental Health Associates on behalf of the U.S. Chemical Manufacturers Association is the largest and most informative investigation thus far undertaken." Sir Richard Doll Scand J Work Enviorn Health 1988; 14:61-78 GGB 3/15/94 SL 107238 BENEFITS OF UPDATING INTER-INDUSTRY STUDY OF VINYL CHLORIDE WORKERS Product Stewardship - Demonstrates to workers, community residents, customers, and other audiences our collective commitment to characterize cancer risks associated with employment in VCM/PVC processes. Scientific Knowledge - Refines the estimate of the number of cases of human angiosarcoma of the liver (ASL) associated with operating VCM/PVC plants in the pre-1972 era in North America. - Provides basis for refining human cancer risk assessments which are used by government agencies for permitting facilities, etc. - Contributes ASL cases to the international registiy. - Helps to resolve unanswered questions about alleged links to cancers of the brain, lung, and hematopoeitic system as well as address non cancer causes of death such as emphysema. Litigation Defense - VCM/PVC manufacturers continue to face toxic tort litigation alleging that numerous other types (non-ASL) of cancer are related to VCM/PVC employment. This type of research is useful in defending such litigation. GGB 3/15/94 SL 107239 INTER-INDUSTRY STUDY OF VINYL CHLORIDE WORKERS (cont.) Chlorine Issue - VCM/PVC continue to be a part of the general debate on health and environmental impacts of chlorinated organics. This type of research serves a valuable role in helping to debate the issues on the basis of good science. GGB 3/15/04 SL 107240 A MADELEINE NASH/CHICAGO TEALTHY AS A PIRATE SUPPING FROM A COVE, the cancer cell severs the moorings that attach it to surrounding tissue. Slowly it extends Sone, two, three fingerlike probes and begins to creep. Then it detects the pulsating pres ence of a nearby capillary and darts between the cells that compose the blood-vessel wall. It dives into the red river that courses through lung and liver, breast and brain. An hour or so later, it surfaces on some tran quil shore, settles down and--at the expense of its hap less neighbors--begins to prosper. Gradually the cancer cell invades the turfoccupiedby its normal counterparts, killing all those in its path. It tricks nearby cells into forming food-bearing blood ves sels, then compels them to chum out growth-spurring chemicals. To shield itself from patrolling immune cells, the cancer cell sprouts spiny armor like a sea urchin s. To expel the agents physicians send to kill it, the cancer cell iloys along its membrane a battery of tiny pumps. Is there a way to fight such a foe? Until now, medicine has tried to overwhelm the can cer cell with brute force, slicing it out with surgery, zap ping it with radiation or poisoning it with chemotherapy. AH too often, however, a few cells manage to survive the onslaught and germinate, sometimes years later, into tu mors that are impervious to treatment The ability of the cancer cell to outmaneuver its attackers has long been re flected in mortality statistics. Despite gains made against cancers such as childhood leukemia and Hodgkins lymphoma, the overall death rate remains dismally high. This year more than half a million Americans will succumb to cancer, making it the nations second *.& SCIENCE SL 107241 ?: V. SL 107242 / M Bbng killer after cardiovascular disease fMet despite the continuing casualties, ere is reason to believe the war against cancer has reached a turning point. During the past two decades, a senes of stunning MALFUNCTION EESp pressor gene that Alexander Kamb and his colleagues discovered may explain why these melanoma cells went astray. discovenes has pned open the black box that governs the behavior of the cancer cell ic bullet they have long been seeking and revealed its innermost secrets. Now Equally tantalizing was the article pub the insights gleaned from basic research lished in Science b> molecular biologist are being translated into novel approaches Alexander Kamb and his colleagues at to cancer therapy. It still looks difficult to Myriad Genetics, a Salt Lake City, Utah, eradicate malignant cells, but scientists are biotech firm A majority of cancer cells, exploring ways to tame them, to make : they found, lack functioning copies of a them behave and thus greatly prolong the gene that serves as a circuit breaker and lives of people with the disease. The new i shuts down the abnormal cell growth that therapies carrv the promise of being not j causes malignancy Already Kamb ls onlv more effective than the current slash- [ dreaming up war's to fix this xeemingh and-bum strategy but also much gentler to simple glitch "The route to therapx" he the patients who must endure the treat says, "seems surprising!) clear ' ment. Exclaims Dr. Dennis Slamon. a ucla cancer specialist1 "This is the most exciting GOOD GENES GONE BAD The conceptual time imaginable!" revolution that is just now sweeping into The excitement was running especial the clinic began m the 196Us when re ly high last week, as encouraging news searchers started to realize that cancer is a poured out of several labs all at once. From disease of dxa, the master molecule that Thomas Jefferson University in Philadel encodes the genetic senpt of life. One of phia came word that an experimental vac dna's most important jobs is to govern cell cine had given patients unusualh long division, the process b\ which a cell makes remissions from advanced melanoma, a a cop\ of itself and splits in two, Ordinari deadls form of skin cancer From Canada's ly. cell division w titiitb regulated but a Nlc.Mister l mxersitx came a report ldenti- cancer cell divider nncontrollabl), pushing f^^ a telltale e ni'vme found m cancer into surrounding tiwue ^^R-but conspicuoush absent from most A pixoUi dix(' )' r. 1 amt- m 197b w fieri ^Wlui cells It cam cr 'VM-archers can find Drs I Michael riirt,op and I larold \ arnuis . was to dcactn ate - this en/\ me, known as at the l mxersitx o t < .ulllorma. San franci1'- t-'iomeras-' the\ mas at 1,-g; ha\e the mag- eo. made a startling iv rvation The\ saw that a viral gene known to cause cancer in chickens was practically a carbon copy of a norma] gene found in animal and human cells. The virus had somehow stolen a per fectly good gene and put it to bad use. This finding helped lead to a general conclusion: cells become cancerous because their nor mal genetic machinery goes awry. The cul prits that initiate the damage can be virus es, radiation, environmental poisons, de fective genes inherited from parents--or a combination of all of the above 1 DNA contains ' oncogenes and tumor-suppressor genes In a normal cell these genes work together to control cell growth nwt ihagw by we Lwn SL 107243 Bv last week researchers had found perhaps 100 cancer cenes. at least three dozen of them important in human tu mors Some known as oncogenes, turn on cell division, whereas others, called tumor- suppressor genes, are responsible for switching the process off In their normal form, both kinds of genes work as a team, enabling the body to perform such vital tasks as replacing dead cells or repairing defective ones But mutations m the chem ical makeup of these genes, whether inher ited or acquired later in life, can disrupt these finely tuned checks and balances. A cell containing a faulty oncogene is often ' likened to a car with a stuck accelerator, a , cell with a damaged tumor-suppressor gene to a car with no brakes. [ Scientists have thus stripped away can cer's mystery and revealed the malignant cell for what it is, not an intrinsically evil villain but an ordinary machine that has broken down in very specific, and poten- 1 bally reparable, ways. They have studied the life history of a cancer cell and found er rant genes at almost every step of the way, from the mibal formation of a tumor to the advanced stages of metastasis, the lethal spread of the disease through the body. : FATAL FLAWS Cancer is not a modem dis ease. Some of our apelike ancestors un- | doubtedly suffered from it. so did the I dinosaurs. In fact, says Robert Weinberg, a molecular biologist at the Massachusetts Institute of Technology, "it is a risk all mul ticellular organisms run." Each time a hu man cell divides, it must replicate its dna a biochemical manuscript some 3 billion characters long. In the course of transcrib ing such a lengthy document, even a skilled typist could be expected to make mistakes, and cells, like typists, occasionally err. More often than not, the mistakes they make are minor and quickly repaired by Johns Hopkins and Boston - Dana-Faroe: proteins that serve as miniature mechanics Cancer Institute have identmed tour new Occasionally, though, cells with detects in genes associated with a torn, ot eariv onset their DNA will continue to divide eventual colon cancer known to afflict particular ly forming small growths The more cell- families These genes are carried bv as division cycles an organism undergoes, the many as 1 in e\ erv 200 Americans, makinc more likely it is to accumulate colonies of them the most common cause of cancer abnormal cells, each the offspring of a sin suscepbbilitv yet discovered In their nor gle progenitor. By the time humans reach mal form, these biological versions ot com middle adulthood, then, their bodies con puterized spelling checkers produce pro tain millions of cells that have taken at least teins that scoot alone strands of rephcabng one step toward cancer. dna searching for tiny typos. When a pro tein finds an error in one of the words inven so cancer is hardly spelled out b\ dna s four-letter chemical evitable. For example, 50% of alphabet, it flashes an alarm A person Americans will develop at least bom with only one good copy of any of Eone precancerous polyp in then- these genes is fine, until some cell m his or colon at some point but only a her colon loses or mutates its backup copy fraction of such polyps will devel Without a spelling checker, mutation piles op into aggressive tumors. Why? upon mutabon. telescoping the time it Usually it takes so long for colon takes for cancer to develop cancer to unfold that most people end up dying of other causes. Indeed, contraBrEyNtTo OUT OF SHAPE Cancer-causing mu popular percepbon, getting cancer is tnaotitoants can occur quite by accident. But all easy. To begin with, a cell must acccuhmrounic exposure to carcinogens--chemi late mutabons not in just one or two genes cals whose by-products bind to dna and but in several. In the case of colon cancer, damage it--greatly accelerate the rate at Dr. Bert Vogelstein and his colleagues at which dividing cells make errors. Proven Balbmore's Johns Hopkins Oncology Cen carcinogens include asbestos, benzene and ter have shown that a cell must sustain some ingredients of cigarette smoke. Many damage to at least three tumor-suppressor carcinogens, it turns out. are not blunder- genes and one oncogene. The first muta- busses but leave highly individualized fin bon spurs the growth of the cell, triggering gerprints m the dna they touch. At the Na the formabon of a benign polyp. Later tional Cancer Insbtute, Dr. Curtis Hams, a changes cause the polyp to expand and be molecular epidemiologist, has been exam come increasingly irregular in shape. By ining cells from liver- and lung-cancer pa the bme a cell in this growing mass suffers tients, searching for mutabons in a tumor- a final, fateful hit to its dna many decades suppressor gene known as p53 (p stands for may have gone by. the protein the gene makes and 53 for the Clearly, however, some people are at a protein's molecular weight). Smokers who much higher nsk of developing cancer develop lung cancer, Hams has found, than others, and at an earlier age. For show bny alterations in the p53 gene that them, heredity plays a major role. Over the differ from those in nonsmokers. They also past five months, compebng teams at vary from the changes found in Chinese 2 Defects in these genes, either inherited or caused Dy radiation, chemicals or viruses, eventually let the cell grow into a tumor. 3 More mutations may cause the cells to become malignant 4 The malignant cells stop producing a chemical that prevents blooo vessels from forming New capillaries then grow into the tumor, providing it with nutrients This alsc creates a route for malignant cells to break away from the main tumor mass and travel to other Darts of the body, where they start new cancers. 5 Chemotherapy can kill the malignant cells, but if there is even one cancer cell that is resistant to the treatment, it will survive and grow into a new tumor This new cancer will be impervious to the treatment SL 107244 riMF, M5RH -T' .H'f, 1 r-caneer patients. In the latter group, Samuel Brodei director of the National age rapidlv and eventualh it dies. Cancer ttoxin, a fungal contaminant of food, is Cancer Institute, "it must contain within carcinogen, and it alters DNA m an ex its cells the knowledge that they have to quisitely precise way, substituting in a sindie But the cancer cell divides at all cost. cells, in contrast, have learned to stop the ticking of the telomere clock. According to research published last week in the Pro gle location a T (thymine) for a G (guanine)It's forgotten how to die" ceedings of the National Academy of Sci in dna's four-letter chemical alphabet. The tumor-suppressor gene p53 is of ences bv Calvin Harley and colleagues at How can such a small mistake--the ten described as "the guardian of the McMaster University in Hamilton, On equivalent of changing the spelling of genome" because it keeps watch over dna tario. malignant cells foil the clock by pro Smith to Smyth--have such an impact? during cell division. When damage occurs. ducing an enzyme--telomerase--that pro Each three-letter ``word" of a gene "sen- \ p53 commands other genes to bring cell di tects the length of the telomere chains. In fence" spells out the instructions for pro vision to a halt. If repairs are made, then essence, telomerase makes the cancer cell ducing 1 of 20 amino acids, compounds { p53 allows the cell cycle to continue. But in immortal. that in turn link to form proteins. A change some cases, if the damage is too serious to in just one letter can result in the subshtu- be patched, p53 activates other genes that A CALL FOR BLOOD Perhaps the most crit bon of one ammo acid for another. The cause thertell to self-destruct. Mutations in ical stage in the life of a tumor comes after new amino acid will be larger, ,, it expands to about a million smaller, staffer or more elastic | cells. At this point, it is "much than the correct one. In ways ' smaller than a BB," says Dr. Ju radical and subtle, it will affect st dah Folkman of Harvard Med- the shape of the protein and its S ical School. This tiny mass-- activity. For if a cell is like a fac 5 known as a carcinoma in situ, tory, then a protein is a cog in a i literally cancer in place--is ma- machine that may have as many i lignant, but not yet dangerous, as 50 components. "If one of ,, Why? Because the cells at the them develops a lank in its ; center of the tumor are too far structure," says Hams, "then from the bloodstream to obtain the machine doesn't fit together as well" sSfifiSk | essential nutrients, they are less - vigorous. Like a society with Kinks in proteins that form zero population growth, a carci- the nuclear matrix--a dynamic l noma m situ adds about as many scaffold to which dna is at " new cells as it loses old ones, tached--may be particularly di- t Months, years, even dec Jlical The reason cancer s' ades may pass. Then an omi- Is typically have a swollen - nous transition occurs. Some and misshapen nucleus, be s cells in the tumor begin secret- lieves Johns Hopkins molecular : ing chemicals that attract en- biologist Donald Coffey, is that ; dothelial cells--the key compo the proteins that form the nu nents of blood vessels. These clear matrix are misaligned in cells form capillaries that grow some fashion. Inside the matrix, into the tumor. They also pump notes Coffey, 50,000 to 100,000 loops of dna are coiled like a Slinkv, but the length of the loops, and where thev begin and end, vanes from tissue to bssue The genes closest to the matrix are those that a particular cell intends to have turned on. IMMORTALITY on chromosome tips act as molecular clocks- Calvin Harley has found how cancer cells stop the ticktock. out molecular messengers called growth factors that stimulate the tumor to divide more quickly. What triggers blood-vessel formation, or angiogenesis, as the process is known? A major factor, scientists believe, is a sudden Genes meant to Stay inacbve are much far drop m the cancer cell's production of ther away. The conclusion is inescapable: a p53, which have been detected in more j thrombospondin, a protein that inhibits mutation in a gene that changes the archi than 50% of all human cancers, are thus ex- i the growth of new blood vessels. In the tecture of the nuclear matrix could wreak tremely dangerous. In laboratory cultures, normal adult, angiogenesis is not only a hax oc by turning the wrong genes on or off. some cancer cells that possess mutant ver rare event, but one cells strive to prevent, sions of p53 do not die when challenged bv save for special circumstances like wound YEARNINGS FOR IMMORTALITY Normal antitumor agents, while those that have ; healing. For blood vessels invading joints cells do not live forever. Under certain cir normal p53 genes go belly-up can cause arthritis, and those invading the cumstances, cells are actually programmed ; Healthy cells apparently have a precise rebna of the eye can cause blindness. To to die One of the most fascinating features j system for ensuring their mortality; short prevent such damage, cells keep blood ves of early development, for example, is the : strips of dna known as telomeres seem to sels at bay by pumping out throm explosive proliferation of certain types of provide a molecular clock When a cell is bospondin. At a recent scientific confer cells, followed by mass suicide. Human young, it has more than a thousand telo ence. Noel Bouck, a molecular biologist embryos start with paddles for hands: it is meres strung along the ends of chromo from Northwestern University Medical cell death that gives them fingers Neurons somes like beads in a necklace. Each time School, stunned her colleagues by present also expire by the billions as the brain re a cell divides. 10 to 20 telomeres are lost, ing preliminary data suggesting that fines lbs circuitry during development In and the necklace grows shorter, Eventual- thrombospondin production max be regu ^^ilts, the cell-death program serxes as a ^ri disciplinarian Cells that become lr ^PparabK damaged are expected to fall on Iv alter m.inv cell divisions, the necklace becomes so short that the cell tails an in ternal hcaltti check designed to keep old, lated b\ that ubiquitous gene. p53 PULLING UP STAKES Autogenesis >s the their swords tor the greater good of the or possible damaged cells front reproducing harbinger ot metastasis The same vessels ganism "For an animal to live," sa\s Dr Result cell cmision stops, the cell begins to that teed the tumor also provide it with ax- SL 107245 malfunctions When she introduced a nor mal nm23 gene jnm stands for nonmetastatic) into highly malignant human breast cells, then miected these cells into mice, their tendency to form metastases dropped as much as 90% GUARDING THE MASTER SWITCH Until last week, p53, the subiect of some 1.000 scien tific papers in 1993 alone, was considered the most important cancer gene The )Our- nal Science even named it Molecule of the Year. But now there is a new contender for notoriety--mtsi. as Alexander Kamb and his colleagues refer to the multiple tumor- suppressor gene they have just discovered. "Multiple" refers to the fact that defects in this gene can cause many lands of cancer, including melanoma, lung, breast and brain JACK SWEPSTON, 48. Pancreatic Cancer. On March 31 this Dallas dentist trav tumors. In fact, functional copies of mtsi eled to the National Cancer Institute in Bethesda, Maryland, to receive a new type of anticancer vaccine. Prepared by a team of researchers, including Drs. David Carbone and John Minna of the University of Texas Southwestern Med may be missing in more than 50% of all hu man cancers. What makes mtsi so significant is its clear role in the cell-division cycle A cell di ical Center, the vaccine was a synthetic version of a mutant protein fragment vides not at will but m response to specific found in Swepston's tumor. The hope is that the immune system will leam to recognize this target and destroy the cells that make it. "1 haven't felt a signifi cant improvement yet," he says, "but the doctors are tremendously excited." signals, such as growth factors produced by white blood cells rushing to repair a wound. These signals are picked up by re ceptors on the membrane of the cell and passed along--like batons in a high-speed enues of escape. Not all the myriad cells ulate new areas. But while an embryonic cell relay--through the interior, all the way to a shed by tumors survive the turbulent voy- stops proliferating and matures mto adult master "on" switch positioned deep in the trough the bloodstream, notes exper- tissue, the cancer cells just keep dividing. nucleus. Not surprisingly, many onco tal oncologist Ann Chambers of the One reason for the difference mav he m London Regional Cancer Centre in Onagene known as nm23, first identified by tario. But those that do eventually slSipteeg in 1988. It seems to help mature cells genes, including one called ras, the first human cancer gene ever identified, are in volved in this type of signaling pathway. through blood-vessel walls with ease. Usinsgtop dividing and arrange themselves in an But there are other molecules that deter a video camera attached to a microscopic orderly fashion. Steeg's research suggests mine whether the cell should heed these lens. Chambers has watched m wonder as that in cancer cells this crucial gene often i signals. And the small protein produced by melanoma and breast-cancer cells, injected j into mice, become lodged in capillary walls, then crawl out into the liver. Three days later, her camera resolves the spidery shapes of tmv metastatic growths. The les son, Chambers believes, is depressingly clear. Cancer cells zip in and out of blood THE BIG KILLERS EEssttiimmaatteess iinn tthtiee UU..SS.... 11999944 Cancel Deaths Long let nnn F'surS New cases rate i ft r\c\r\ i 172,OUU Risk Factors Cigarette smoking; exposure to asbestos. Chemicals, radiation, radon vessels so readily that, once angiogenesis occurs, they should be presumed to have al- j ready spread around the body. Metastasis is an event of awesome com plexity one that requires multiple genes to cooperate as closely as musicians in an or chestra. Some of these genes code for chem Pancreas 25,900 27,000 3% ical solvents that enable the advancing cell to dissolve surrounding tissue. Others order up the produchon of adhesion molecules j that like treads under a tank, move the cell i . Hn/ininn't -- Lymphoma . 22,750 Non-Hodgkin s Ile--roXg._t_iuIa. tLotJ.llWooJ 7O0/ 52,900 52% 2e,DeUnUn ooni Reduced immune function, exposure to herbicides. solvents, vinyl chloride ioGneiznientgicraabdniaotriomna,lictiheesm, eicxaplso,suvrierutsoes forward. Why would genes do that? The an swer. notes Patricia Steeg of the National 13,600 24,000 39% nfpregna^s0^ ene"C d,sorders Cancer Institute, is that while the genes im portant to metastasis are abnormally turned on the\ are not necessanh abnormal them- A cancer cell, in many wavs, is not tdim-run! trom an embryonic cell on its v K-commi; a patch of skin or a bundle KMney Bladder 11,300 27,600 55% Smoking 10,600 51,200 79% rvirai . ^ G7V, 10,500 46,000 *4TM oomemai________________________ OAto Smoking -- Intercourse at an early age; multiple sex partners, smoking Eariv menarche, late menopause, obesit res Pod; embivoTiK' and cancer cells 7,925 29,600 53% Smoking: excessive use of alcohol mviue and term ill-defined clumps Both cet Skin Melanoma up ano move around Both migrate and pec soura-Anwa.jmiSoon, e onn to nnn oaoc Sunnurn. fair complexion, exposure (o ''uu M,wv *"TM coal tar, pitch creosote, arsenic, radium SL 1 0 7 2 4 6 mtsi appears to he among the most impor- j tant inhibitors of cell division Last year re- 1 searchers at New York's Cold Spring Har- ! bor Laboratory discovered that a protein thev called pl6 stifled an enzyme that is a growth promoter. Last week it became clear that pl6 and the mtsi protein are one and the same, TARGETS FOR CANCER FIGHTERS Theo retically, any gene that goes awry in a can- j cer cell offers a way to attack the problem, But those that directly influence a cell's de cision to divide are spurring particular in terest. The protein made by the mtsi gene seems exceptionally promising, for it has characteristics suggesting it may be easily fashioned into a drug, which then might be able to stop tumor cells in their tracks. "In terms of therapeutic potential," declares Kamb, "mtsi may be the most important tumor-suppressor gene yet discovered." Still, as pharmaceutical companies well know, many surprises can pop up on the way to developing a new drug, and oth er approaches to cancer therapy may win out in the end. Among the possibilities are anticancer vaccines designed to stimulate ANN FAGAN, 37, Colorectal Cancer Ten years ago, when Ann Fagan, a paralegal the immune system to combat tumors. Currently being tested in the U.S. and Canada is a vaccine that spurs an assault on the weirdly configured carbohydrates that from Conyngham, Pennsylvania, was found to have cancer, she underwent an ileostomy, a procedure that constructs an opening for the bowels through the abdominal wall. Last year tests revealed that her daughters Katie (left), 13, and protrude from tumor cells like spikes on a Sarah, 11, had inherited a genetic defect that puts them at high risk for the same medieval ball and chain. At the meeting of type of cancer. But this diagnosis has a silver lining, since the girls will be able the American Society for Cancer Research last week. Dr. David Berd of Thomas Jef ferson University presented the most en to have surgery before rather than after cancer develops. Cancer susceptibilities that come from inherited mutations may account for 20% of all cases. couraging evidence to date that the vaccine strategy may work. Berd told of inoculating because the process is so rare in normal i future already exists, "After all, we don't 47 melanoma patients with a vaccine made cells. Clinical tnals have begun on several cure diseases like diabetes and hyperten of their own tumor cells inactivated by ra compounds that interfere with angiogene sion," says Dr. Lance Liotta. the National diation. Three years later, 60% remained sis. One such compound comes from a fun- ! Cancer Institute's leading metastasis ex tumor-free, compared with 20% in the un- gus that was accidentally discovered m pert."We control them Why can't we look vaccmated control group. The approach 1989 when it contaminated cultures of en at cancer that wav?" works best, apparently, m patients who dothelial cells m Judah Folkman's Harvard By this reasoning, even metastatic- have tumors small enough to be surgically laboratory, dramatically curtailing their cancer may eventually be brought to heel. removed but whose disease shows signs of growth. This drug, says Folkman, is aimed Squeezed into a tiny cubicle day after day spread not at cunng cancer but at prolonging the at the National Cancer Institute, Patricia The discoverv announced last week period of time colonies of tumor cells Steeg stares at colonies of aggressive that cancer cells rely on the enzyme telo- missed by conventional therapy remain in breast-cancer cells that have shut down merase to stay alive opens up a different at place without spreading "Suppose we pro the protective nm23 gene. Soon she will tack strategy The leader of that research long this period of dormancy for 10 vears, i squirt over these colonies newly identi team, Galvan Harley, has taken a leave from and then another 10 years," muses Folk- fied antitumor compounds. Among them McMaster University to work at Geron Corp, in Menlo Park, California. The com pany is trying to craft a drug that will block man "Why, now we re beginning to com- \ she hopes to find one, maybe more, that pete with the normal life span" j interferes with metastatic growth A total Indeed, what seems most significant ! of 14 of these compounds are already sit the action of telomerase. "The cancer cell," about all the new therapies, what )oms explains Harley, "is already very old. If we them together, is not their power, for this can inhibit telomerase, we might cause the has yet to be proved Rather, it is the seis tumor to die after a few doublings" Even I mic shift in strategy1 they collectively repre better, the fact that cancer cells produce sent Increasinglv, researchers speak not of telomerase and that normal cells (save for , slaughtering the cancer cell hut of tricking sperm) don't, says Harley, "gives us hope j it into dving naturally, perhaps of old age. that we may be able to develop a drug with as other cells do Thev .dso talk of leining in out serious side effects " the cancer cell, even rehabilitating it, a task The formation of blood vessels in a tu- that demands the development ot less tox itioi through angiogenesis is another ic drug, dial can in loicutod ovei a life promising target for an anticancer drug- time Ih`- modi1! loi cancer tiiciapv of the ting in a freezer in her lab--white crystals that cluster like snowflakes in the bottom of test tubes II these fail to have an ef fect, Steeg has a list of more than 30 others that might. Like many cancer re searchers, she convevs. through her own personal enthusiasm a sense that an im mense psychological barriei has been breached No, Steeg has not vet tound a drug that cures cancer or even controls it But, she exclaims "1 in beginning to like the odds" tn c1 11 M i" 61