Medical Examiner

Your Health This Month

Germs that make you fat, cloned cows that won’t make you sick, and the latest wonders of Botox.

This month, Dr. Sydney Spiesel discusses cattle engineered to be free of mad cow disease, a once-and-for-all flu vaccine, fattening bacteria, and Botox as a cure for writer’s cramp.

Safe beef

Disease: As my vegetarian friends delight in reminding me, Creutzfeldt-Jakob disease, which attacks and eventually destroys the brain, can be transmitted to humans who eat beef from cattle infected with bovine spongiform encephalopathy, or mad cow disease. Both BSE and Creutzfeldt-Jakob are thought to be caused by something really weird: not a virus, bacterium, or parasite, but a prion—a normal protein called PrPR whose function is unknown, and which becomes infectious when its structure changes because it has misfolded.

Question: What would happen if you used the tools of molecular biology and animal cloning to produce cattle that lack the PrPC protein? Could such an animal survive? What effect would the absence of PrPC have on it?

Answer: Drs. Yoshimi Kuroiwa and James Robl of the biotech firm Hematech and Jürgen Richt of the United States Department of Agriculture have come up with an answer: The cows seem to develop in a completely normal way, unaffected by the missing protein. More importantly, laboratory studies showed that their brain tissue did not allow for the development of prions. This makes it extremely unlikely that beef or products made from animals like these could cause Creutzfeldt-Jakob disease in humans.

Implications: This discovery could have even broader import. Hematech is trying to use biotechnology to develop cattle that produce large quantities of human antibodies directed against specific diseases. Normally, when cow or sheep or horse antibodies are used to treat or prevent human disease, our bodies soon recognize them as foreign and become allergic to or inactivate them (or both). But if cows could produce human antibodies, they would not be deemed foreign and our bodies would not reject them. It would be especially reassuring if these antibodies could be produced in prion-free cattle like the ones described by Kuroiwa and colleagues, since products from those cows couldn’t pass on Creutzfeldt-Jakob disease to humans being treated with them.

Bonus: My own interest in all of this is more primitive. I’d just like to go back to eating a few beef products—cervelles au beurre noir, for instance—presently considered too risky for dinner. How perfect that the Food and Drug Administration just issued a report on the safety of cloned meat for human consumption!

A one-shot-forever flu vaccine?

Problem: I’m tired of giving flu shots, worrying about my annual vaccine supply, and (most of all) of the possibility of an avian influenza pandemic. Wouldn’t it be great if we could come up with a universal vaccine—one that covered all strains of flu virus and could protect us even against new and dangerous mutations like the H5N1 bird flu?

New research: Current vaccines target structures on the surface of the flu virus, large molecules that promote attachment and penetration of the virus to the human cell. Unfortunately, these structures are the very ones that mutate so readily and for that reason make last year’s vaccines useless. But there is another possible molecular target: the “M2” protein, also found of the surface of the virus, and much less likely to mutate. Walter Fiers and his research group at Ghent University in Belgium have been looking for years into a vaccine directed against M2. A recent paper by Fiers, Marina de Filette, and their co-workers describes promising results—though limited to mice—for an M2-targeting vaccine that’s administered in a nicer way than usual: by nasal spray.

Results: The vaccine’s special feature is that it contains an adjuvant— an additive that enhances the immune response —in addition to an ingredient that stimulates a strong specific immune response to the M2 protein of influenza. In the Belgian experiments, the vaccine-adjuvant combination, sprayed up the nose of mice, completely protected animals exposed to live influenza infection against death and significantly ameliorated their signs of illness. The experimental adjuvant chosen caused no toxic side effects in mice, though it has not yet been tested in humans. It works as an adjuvant for many vaccines, not just flu, so we might look forward to other kinds of nasal-spray vaccines containing it.

Conclusion: If it works as well and as safely in humans as in mice, this vaccine might turn out to be just what we need to protect us from ordinary flu, year to year, and also against new and virulent forms of flu as they arise. What a concept.

Germs that make you fat

Gut feeling: For the most part, we only pay attention to the bacteria in our guts when they attack us with, say, a bout of Montezuma’s revenge. But the germs inside of us may affect us every day—by helping to determine our weight.

New research: Two recent papers from the laboratory of Dr. Jeffrey Gordon at Washington University in St. Louis, one whose lead author is Peter Turnbaugh and the other whose lead author is Ruth Ley, are beginning to unravel this phenomenon. Many of the gut bacteria are representative of two large groups of germs: the Firmicutes (which roughly overlap with the Gram-positives of high school biology) and the Bacteroidetes (typically Gram-negative bacteria, which grow without oxygen and are usually sort of smelly). There are other germs in the bowel, as well, but Gordon’s group has been particularly interested in the balance between these two large divisions of intestinal bacteria.

Findings: Studying mice that are genetically predisposed to obesity or leanness (but are otherwise similar), the researchers found that fat mice had an abundance of Firmicutes while their lean littermates had more Bacteroidetes. Here’s one reason why: When the bowel in a mouse is inhabited by lots of Firmicutes bacteria, the animal harvests energy from its diet more efficiently. So the same amount of food that fattens the Firmicutes-carrying mice leaves the Bacteroidetes-carrying mice slim. More provocatively, when Gordon’s team took germ-free, normal-weight mice and infected them with Firmicutes-predominant bacteria taken from obese mice, they fattened up—whereas similar littermates colonized with intestinal bacteria taken from lean mice did not. Something similar seems to occur in humans: The ecology of the bowel shifts toward the Firmicutes in heavy people and toward the Bacteriodetes in leaner people (including those who become thin as a result of dieting).

Conclusion: These findings, taken together, strongly suggest that intestinal bacteria may well play a significant role in how animals and humans absorb energy from the food we eat and turn it into body fat. How comforting: Germs, not gluttony, may be the cause of my weight gain.

The benefits of vanity

Problem: Writer’s cramp, or hand dystonia, occurs in about one in 20,000 patients and is characterized by disabling contractions of the finger, hand, and forearm muscles. Though the problem originates deep in the brain, it may be set off by vigorous, repetitive hand and finger work. We don’t know much about writer’s cramp other than that susceptibility is sometimes inherited (some of the genes involved have been identified). The condition has been exceptionally hard to treat. Hypnosis, biofeedback, acupuncture, drugs, splinting, encouraging the use of the other hand, and even neurosurgery have been tried. None have been consistently successful.

New research: Now J.J.M. Kruisdijk and some fellow neurologists at the University of Amsterdam have presented research on a treatment that helped 70 percent of the patients to whom it was given. The method consists of injections into the finger and hand muscles of tiny doses of a British medication, Dysport, which is much like the drug sold in the United States as Botox. Both drugs are purified forms of a toxin produced by the botulism germ.

Findings: In the Dutch study, 20 patients with writer’s cramp were treated with Dysport and 19 with a placebo. Neither the researcher nor the patients knew who got the active drug, and the effects of treatment on each group were measured both subjectively (improvement perceived by the patient) and objectively (improvement in handwriting). The Dysport-treated patients showed better results measured both ways, though a few patients had no response to the medicine and a few others had a positive response but disliked the muscle weakness that the treatment caused. At the end of the experiment, half chose to continue with the injections.

Musicians as well as writers are likely to suffer from hand dystonia and Botox or similar products have helped them, too. For example, the famed pianist Leon Fleisher, in his mid-30s developed writer’s cramp in his right hand so severe that it prevented him from playing the piano with both hands for more than 30 years. Treatment with Botox successfully restored his ability  to play with two hands. It’s a fine, if rare, example of a vanity product being put to serious use.