Johns Hopkins Magazine -- June 2000
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JUNE 2000



In recent years, shark cartilage therapy has emerged as a much-touted popular remedy for cancer, arthritis, and other illnesses--and as
a growing commercial enterprise. Could something fishy be going on? Gary Ostrander
believes so.
S C I E N C E    &    T E C H N O L O G Y

Predators Promise
By Melissa Hendricks
Opening photo by Michael Ciesielski

An advertisement in a Nassau newspaper a few years ago may have been what finally convinced Gary Ostrander to take action. In bold type, the ad for a local aquarium declared: SHARKS DON'T GET CANCER. WHY? NO ONE KNOWS. WE MUST PROTECT THEM.

Ostrander (pictured at top) had been hearing stories about the cancer-defying sharks since at least the late 1980s, when he was studying cancer using fish models at the University of Washington. He felt sure the claims were not true but at first had paid them little heed. The ad for the shark exhibit was the last straw. "Here you had an organization whose mission is conservation and education of the public, and they got it wrong," says Ostrander, who since 1996 has been associate dean for research at Hopkins's Krieger School of Arts and Sciences. So he decided to investigate the allegation in earnest.

By then, an entrepreneur named I. William Lane had widely publicized the alleged benefits of powdered shark cartilage, claiming that it could treat cancer, arthritis, and other diseases. Many companies had begun marketing shark cartilage pills, and oncologists in the U.S. were finding that a growing number of their patients had tried the alternative therapy.

So Ostrander and a colleague combed through the National Cancer Institute's Registry of Tumors in Lower Animals. There they uncovered 40 cases of benign and malignant tumors in sharks and their close relatives--skates, rays, and ratfish. They also scanned the clinical literature, finding no studies in peer-reviewed journals showing that shark cartilage was effective in curing cancer. In April, Ostrander and his colleague, registry director John Harshbarger, reported their findings at the annual meeting of the American Association for Cancer Research, in San Francisco.

Cancer researchers who attended the meeting responded supportively. Many were thankful that Ostrander and Harshbarger had validated what they had long suspected. Others were surprised at the finding, even slightly embarrassed that they had fallen for the original claims. The report also generated interest among the mainstream media. Newsweek, USA Today, and wire services ran stories. And several biologists have called Ostrander and Harshbarger to report new cases of tumors in sharks. Ostrander is visibly outraged by Lane and other marketers of shark cartilage. Lane's data, he declares, is "largely bogus. Sharks are being destroyed needlessly to exploit desperate people, based on erroneous information."

Just another tale of the snake oil salesmen fleecing the gullible masses, right? If only the issue were that clear-cut. The more complicated reality is that while sharks do, in fact, get cancer, the claim that their cartilage has cancer-fighting powers is based on sound science.

One of the researchers who helped build the field of cartilage research is Henry Brem, professor of neurosurgery, oncology, and ophthalmology at the Johns Hopkins School of Medicine. As a graduate student in biochemistry at Harvard 30 years ago, Brem worked under Judah Folkman, a biologist and the chief of surgery at Boston Children's Hospital. Folkman had hypothesized that tumors stimulated the growth of new capillaries, which provided the tumor with a continuing source of nutrients and oxygen. The process of new blood vessel growth, or angiogenesis, enabled the tumor to expand.

Folkman and Brem hoped to find substances that would inhibit angiogenesis. Their search began with cartilage from newborn rabbits. Because this elastic tissue (and all forms of cartilage) lacks blood vessels, they reasoned, it must contain some antiangiogenic substance.

If their theory proved correct, then they would be onto something big--a means of halting tumor growth in its tracks, perhaps even a cure for cancer. This quest consumed them, Brem recalled recently. "We worked around the clock."

Brem and Folkman tested the theory using adult rabbits. They implanted a tumor in one cornea of each rabbit. Next to each tumor, they inserted a small piece of cartilage from neonatal rabbit scapulae. As controls, they implanted in rabbit corneas a tumor alone, or a tumor alongside a piece of cartilage that had been boiled to inactivate any antiangiogenic substances.

Hopkins's Henry Brem did early work showing that animal cartilage inhibited tumor growth. But he calls current claims about shark cartilage, "a distortion of the science."
The difference between the experimental and control animals was like night and day. In the control animals, the tumors rapidly enlarged, covered by a dense network of blood vessels. In contrast, the tumors in the experimental animals stopped growing. The researchers submitted their results to The Journal of Experimental Medicine, which published them in the February 1, 1975, issue. Brem, Folkman, and another young researcher named Robert Langer then conducted similar experiments using partially purified calf cartilage prepared as pellets and coated with a polymer that permitted a slow, steady release of the cartilage. Again, the cartilage inhibited tumor growth. The researchers reported their findings in the July 2, 1976, Science.

Brem soon left Folkman's lab to go to medical school at Harvard. But Langer continued the research. After moving to MIT, he decided to replicate the rabbit experiments using shark instead of calf cartilage. He collaborated with Anne Lee, who later completed her postdoctoral fellowship and residency in radiology at Hopkins (1993). Although Boston slaughterhouses had gladly provided calf carcasses for the earlier experiments--$10 for 100 pounds, Brem recalls--the calf skeletons contained relatively little cartilage. Shark skeletons, by contrast, were comprised entirely of this gristly tissue.

In the lab, Langer and Lee found that implanted shark cartilage pellets did the same thing the calf cartilage had done, inhibiting blood vessels from growing toward tumors. The researchers reported their findings in the September 16, 1983, Science.

Enter I. William Lane. A businessman and biochemist by training, Lane had directed the Marine Resources Division for W.R. Grace & Co. before becoming a consultant and starting his own shark fishing enterprise, according to the bestselling book he co-wrote with Linda Comac called Sharks Don't Get Cancer: How Shark Cartilage Could Save Your Life (Avery Publishing Group Inc., 1992). Lane heard about Langer and Lee's study through a CNN broadcast, and immediately became excited about the therapeutic possibilities of oral shark cartilage.

He also learned about studies conducted by Carl Luer, a biomedical researcher at Mote Marine Laboratories, in Sarasota, Florida. Luer had exposed sharks to high levels of a carcinogen, but the sharks did not develop tumors. To Lane, this result suggested that something about sharks enabled them to resist cancer.

Who's minding
the store?

Between 1990 and 1996, U.S. consumers nearly doubled their spending on dietary supplements, from $3.3 billion to $6.5 billion, according to market research data on a U.S. Food and Drug Administration website. The list includes shark cartilage, saw palmetto, St. John's Wort, and numerous other vitamins, minerals, herbs, amino acids, metabolites, andother substances that are used to supplement the diet but do not qualify as drugs.
   So who oversees the safety, effectiveness, and quality of what's inside those little brown bottles? Partly the FDA. But much of the responsibility rests with consumers and manufacturers.

Safety: Drug manufacturers must show that a new drug is safe and effective before it is marketed--a sometimes lengthy process involving preclinical testing, clinicaltrials, and other steps. In contrast, at least 75 days before a new dietary supplement comes to market, manufacturers need only submit to the FDA a history of the product's safety showing that it will not cause illness or injury if used according to the label's recommendations. Dietary supplements that were on the market prior to 1994 are exempt from this requirement.
   In recent years, a number of dietary supplements have been associated with health problems. But by law, the FDA may not restrict the sale of a dietary supplement unless it demonstrates that the product is not safe.

Efficacy: Manufacturers are forbidden from claiming that a dietary supplement can diagnose, treat, cure, or prevent a disease. If they do, then the product is considered an unauthorized drug. (The FDA has granted certain exemptions: For example, it is allowable to state that calcium reduces the risk of osteoporosis.)
   Manufacturers may, however, make claims about a supplement's effects on the structure or function of the body. So, for example, stating that a product "prevents heart disease" is not permitted. But claiming that it "maintains a healthy circulatory system" is. By law, the FDA cannot require manufacturers to prove structure-function claims.

Quality: Dietary supplement labels must include a list of the product's ingredients in descending order of predominance. But the FDA does not verify this information. Studies have found substantial discrepancies between the amount of active ingredients listed on the label of some products and what is actually in the bottle. One safeguard is to look for products that have the U.S.P. notation, which indicates that the producers followed U.S. Pharmacopoeia standards.

Peddling the promise of shark cartilage to anyone who would listen, Lane believed that shark cartilage held hope for patients with cancer, as well as rheumatoid arthritis and diabetic retinopathy, both diseases involving angiogenesis.

Lane convinced researchers at the Institut Jules Bordet, in Brussels, to conduct their own studies of shark cartilage on laboratory animals. According to Lane's book, the oral shark cartilage stopped tumor growth. Lane had also developed a system for finely pulverizing shark cartilage without destroying its proteins, and in 1991, he received a patent for using specially prepared shark cartilage to inhibit angiogenesis.

But results in humans stirred the most excitement. Lane helped initiate clinical investigations in Mexico, Panama, and Cuba. In the latter study, 27 terminal cancer patients received shark cartilage treatments in the form of a retention enema for several weeks. In the course of the treatment, some patients switched to oral therapy. Almost all the patients improved, according to Lane. For example, an 82-year-old man with metastatic prostate cancer achieved a 58 percent reduction in tumor size and was free of pain following shark cartilage treatment, Lane reported.

Lane garnered widespread attention in 1993 when 60 Minutes ran a story about the use of shark cartilage as cancer therapy. The segment featured Lane and Cuban physicians and patients who had participated in the study. He then co-authored a second book, Sharks Still Don't Get Cancer (Avery Publishing Group Inc., 1996).

Other companies have followed in Lane's footsteps and now market their own shark cartilage pills and powder. Customers are forking over hefty sums for the stuff. A 90-capsule bottle (750 milligrams) of one brand at a natural foods store in the greater Baltimore area sells for $27.99. The label recommends taking eight pills per day--which would mean spending $77 per month. It is difficult, however, to determine the size or wealth of the industry. Andrew Lane, William Lane's son and the president of Lane Labs, refuses to disclose his company's profits. One figure indicates that the world market for shark cartilage products exceeded $30 million in 1995.

Several web sites for alternative and natural health remedies boast of the benefits of shark cartilage therapy. "THIS COULD SAVE YOUR LIFE!" declares one site - "Shark cartilage can help to halt a wide range of cancers dead in their tracks." It goes on to quote Lane: "What we see in patients who take shark cartilage is the effect of prevention of angiogenesis." It also quotes a cancer survivor who says she chose shark cartilage over the surgery, radiation, and chemotherapy that her doctors prescribed.

But the U.S. medical establishment, Lane laments in his books, stubbornly refuses to listen to the evidence in support of shark cartilage therapy.

A distortion of the science," pure and simple, is how Henry Brem views Lane's conclusions.

The clinical studies in Cuba and elsewhere lacked controls, says Brem. "None would meet the standards of what we do in clinical trials here.

"We never showed that the oral form [of cartilage] has any benefit," says Brem. "Because A equals B doesn't mean that C equals D. Because shark cartilage has antiangiogenic activity doesn't mean that crushing it up and swallowing it does."

Shark cartilage is made of proteins, Brem explains, which are broken down by enzymes in the gut. It is unlikely that these active components of shark cartilage maintain their integrity long enough to be absorbed into the bloodstream. Likewise, there is no evidence that proteins in a retention enema would be absorbed.

Further, while no one has shown that shark cartilage can be toxic, Brem and other oncologists worry that it could do harm in other ways. "If patients choose shark cartilage instead of treatments that have proven benefits," he says, "then those patients are potentially shortening their lives." A letter sent to the New England Journal of Medicine a few years ago from a Canadian physician described just such a case. After their 9-year-old daughter had surgery to remove a brain tumor, the girl's parents opted to treat her with shark cartilage, against the advice of physicians who had recommended follow-up radiation and chemotherapy, which the physicians said would accord a 50 percent survival rate. The girl died.

In December 1999, the U.S. Food and Drug Administration sought a permanent injunction against Lane Labs to prevent the company from marketing BeneFin, its brand of pulverized shark cartilage, and two other healthcare products. The agency stated that Lane Labs had made unproven claims about Benefin pertaining to "the cure, mitigation, treatment, and prevention of cancer and other diseases, including rheumatoid arthritis and osteoarthritis." In other words, according to the FDA, Lane Labs was making claims that would define Benefin as a drug rather than as a dietary supplement. But the FDA had not approved it for that purpose.

At the same time, the National Center for Complementary and Alternative Medicine, a branch of the National Institutes of Health, is sponsoring two clinical trials. The first, now being conducted at the M.D. Anderson Cancer Center, at the University of Texas, in Houston, is testing a liquid shark cartilage extract developed by Aeterna Laboratories. The study, with initial funding of $748,892, involves 756 lung cancer patients and will take about three years.

The second study, a $1 million-plus investigation based at the Mayo Clinic in Rochester, Minnesota, will test Lane Labs' Benefin in patients with breast or colorectal cancers. As of April, however, the study was on hold while Lane Labs dealt with the FDA suit.

As a biologist, Ostrander worries about a growing shark cartilage industry that could lead to overfishing: "I can appreciate what kind of damage is caused anytime you remove the top level of predator from an ecosystem."

Both trials are being administered through the National Cancer Institute.

The fact that the NIH is supporting clinical studies of a substance that lacks significant preclinical data irks some oncology researchers. In response, Jeffrey White, who directs the Office of Cancer Complementary and Alternative Medicine at the NCI, says there are pragmatic reasons for conducting the studies. "Shark cartilage was chosen largely because of the tremendous utilization by cancer patients," he says.

Even Hopkins's Brem can't argue with that logic. Many of his patients tell him they've tried shark cartilage. "Desperate people do desperate things," he says. "If it's being used clinically, it should be evaluated." It's particularly important, he notes, to ascertain whether such alternative therapies could conflict with conventional treatments such as chemotherapy and radiation.

"It's ridiculous to say sharks don't get tumors because nobody ever looked," says Harshbarger. "Many more tumors would be found if sharks were systematically surveyed."
Clinical evidence or the lack thereof is not the only reason for the clinical trials of shark cartilage. There is also that notion that sharks do not get, or rarely get, cancer. In explaining the need for further research funding on sharks and their relatives, the House and Senate Appropriations Committee began with this clause: "The committee notes the unusually low incidence of cancer in sharks, skates, and rays."

To Gary Ostrander, that premise lacks any sort of scientific foundation.

Ostrander and Harshbarger's search of NCI's Registry of Tumors in Lower Animals clearly shows that sharks get cancer. The Registry includes literature on and specimens of tumors in cold-blooded animals. Ostrander and Harshbarger identified two previously undescribed cancers in sharks--a kidney cancer in a dogfish and a blood cell cancer in a sandbar shark. They also found three tumors of the cartilage--calling into question the supposition that shark's cartilage protects the animals against cancer--and tumors in every other organ system except the respiratory system. About a dozen were malignancies.

Lane admits there have been cases of cancer occurring in sharks but contends that the numbers are "insignificant." He writes in his book, "...while ALMOST No Sharks Get Cancer might have been a bit more accurate, it would have been a rotten title." "That's propaganda 101," replies Ostrander. He and Harshbarger say that no one knows whether sharks have an unusually low rate of cancer.

"There has never been a definitive study," says Harshbarger. "It is ridiculous to say that sharks don't get tumors, or get a lower rate of tumors, because nobody ever looked. We believe many more tumors would be found if sharks were systematically surveyed." The Registry is simply a repository that accepts all reports of tumors, including those noted by the layperson.

He also notes that there could be many explanations for Carl Luer's inability to induce tumors in sharks at the Mote Marine Labs. Luer's group may have chosen a chemical that does not cause tumors in sharks, for example. "There are thousands of carcinogens out there," says Ostrander, and not every one causes cancer in every animal. Even Luer, who is continuing his shark studies, has written that there is no evidence that cartilage in any animal confers disease resistance.

Says Ostrander, "Sharks have gotten so much attention, I think, because they are mysterious animals in the minds of the public and they are so large and, as such, there is lots of cartilage. But the fact that they do not present high numbers of tumors has been blown way out of proportion."

He adds that he would not be surprised if sharks did have a lower incidence of cancer than many other fish. Most sharks are pelagic, while fish that grub around at the bottom of the ocean, lakes, or ponds come in contact with sediment where carcinogens lie. "People ask me if I eat the fish from Puget Sound or Boston Harbor," he says. "And I tell them I don't eat the flounder and English sole [which feed on the bottom]. But I have no problem eating the salmon or rockfish."

As a biologist, Ostrander also worries that if the shark cartilage industry continues to grow, the consequences for shark populations could be serious. Sharks are extremely vulnerable to overfishing, he says. Most shark species take a long time to reach sexual maturity--some as long as 20 years--and then only produce a few young before they die. If a significant number are fished, it would take several decades for them to recoup their numbers.

The National Marine Fisheries Service has placed three shark species on the candidate species list, the step preceding placement on the endangered species list. It has also applied its official overfishing designation to approximately 22 species of large coastal sharks in the Atlantic. Many of those species have declined by 80 to 90 percent since the 1970s, according to Mary Camhi, a senior scientist with the National Audubon Society's Living Oceans Program.

"As someone who spends a considerable amount of time reading about, studying, and working in marine ecosystems," says Ostrander, "I can really appreciate what kind of damage is caused anytime you remove the top level predator from an ecosystem."

"Sharks, much like spiders and snakes, are not the most popular animals in the world. However, they are key to keeping the ecosystem in balance. If we took away all the spiders and snakes we would have major insect and rodent problems. We don't know what the outcome will be to remove all the sharks. However, my guess is that it will not be good."

Melissa Hendricks ( is the magazine's senior science writer.