Rewriting Life

Synopsis: Biotechnology

Infections train the immune system to destroy cancerous cells.

Bacteria Defeat Tumors
Infections train the immune system to destroy cancerous cells

Context: Many clinicians and researchers attempt to treat cancer without resorting to debilitating chemo- and radio­therapy. But even “magic bullet” drugs, which hone in specifically on cancer cells, have serious side effects. A better option may be to train a patient’s own immune system to attack tumors. Now researchers at Johns Hopkins University, led by Bert Vogelstein, have found that bacteria show promise as a means of priming the immune system, and might be used to treat cancer of the liver, lungs, and pancreas.

Methods and Results: Animals with cancerous tumors were injected with bacteria that thrive in the oxygen-deprived centers of solid tumors and die off in healthy, oxygenated tissues. The researchers hoped that the bacteria would destroy the tumors from the inside out, leaving an outer rim of cancer cells that could be more easily treated with standard therapies. The bacteria did just that. However, the researchers also found that the infection frequently prompted the subject’s immune system to recognize the cancer and attack it. In 23 of 70 test animals, this immune response destroyed the remains of the tumor without additional therapy. Even after the bacterial infections cleared, the animals’ immune systems attacked newly injected cancerous cells of the type successfully treated. The treatment had similar effects in both mice and rabbits, making it plausible that it could also work in other species, including humans.

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Why it Matters: The ideal cancer treatment, as currently imagined, would kill cancer cells without damaging healthy ones. The Hopkins researchers’ method goes even further, preparing the immune system to defeat cancer cells left behind after a tumor is destroyed. So far, bacterial therapy does not appear to have the side effects associated with current cancer treatments. Of course, many promising treatments in animals have disappointed in human tests. But if the therapy does prove safe and effective for humans, cancer patients could be looking at much more successful and comfortable treatments in the future.

Source: Agrawal, N. et al. 2004. Bacteriolytic therapy can generate a potent immune response against experimental tumors. Proceedings of the National Academy of Sciences 101: 15172-15177.

Trouble in the Cell’s Power Plant
Aging diseases link to a mitochondria gene

Context: If you have high blood pressure, you’re more likely to be obese and to have high cholesterol and a host of other unhealthy conditions. Recent evidence suggests that obesity keeps the body’s cells from responding properly to blood sugar, leading to diabetes. However, why these conditions are associated with high blood pressure is still poorly understood. A team of researchers from Yale University and the State University of New York Upstate Medical University sought an answer in genetics and found one in mitochondria. Most cells contain hundreds of mitochondria, rod-shaped structures that originated billions of years ago when a cell engulfed a bacterium but did not destroy it. Now, the bacterium’s descendants help the body’s cells convert food into energy.

Methods and Results: Frederick Wilson of Yale and his colleagues studied a family with a high incidence of conditions associated with hypertension and tracked inheritance in 142 blood relatives over four generations. After adjusting for differences in age, weight, and medication use, the researchers found a clear pattern of inheritance. All the conditions descended through the maternal line, indicating that the culprit gene was mitochondrial. (A person’s mitochondria derive from those origi­nally present in the ovum and have their own, bacteria­like DNA.) A full sequence of affected family members’ mitochondrial genome revealed 14 differences from standard sequences. Thirteen had been previously reported to have no impact. The 14th was new and was mapped to a gene for a transfer RNA, a molecule essential to building proteins. In fact, the gene is constant across animals, fungi, plants, and even bacteria.

Why it Matters: Against a noisy backdrop of studies showing how heart disease, depression, and other complex diseases can be attributed to small effects from many genes, Wilson and his colleagues’ research shows that a single gene can be tied to many disease-associated conditions. More importantly, the research pins responsibility for several diseases on mitochondria, whose function declines with age. Those seeking the fountain of youth, or just hoping to stave off the ravages of old age, may benefit from further studies of these vestiges of ancient bacteria.

Source: Wilson, F. H. et al. 2004. A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science 306: 1190-1194.

Embryonic Stem Cells Made Easy?
A technique for creating stem cells may be less labor intensive—and less controversial

Context: If you have high blood pressure, you’re more likely to be obese and to have high cholesterol and a host of other unhealthy conditions. Recent evidence suggests that obesity keeps the body’s cells from responding properly to blood sugar, leading to diabetes. However, why these conditions are associated with high blood pressure is still poorly understood. A team of researchers from Yale University and the State University of New York Upstate Medical University sought an answer in genetics and found one in mitochondria. Most cells contain hundreds of mitochondria, rod-shaped structures that originated billions of years ago when a cell engulfed a bacterium but did not destroy it. Now, the bacterium’s descendants help the body’s cells convert food into energy.

Methods and Results: Frederick Wilson of Yale and his colleagues studied a family with a high incidence of conditions associated with hypertension and tracked inheritance in 142 blood relatives over four generations. After adjusting for differences in age, weight, and medication use, the researchers found a clear pattern of inheritance. All the conditions descended through the maternal line, indicating that the culprit gene was mitochondrial. (A person’s mitochondria derive from those origi­nally present in the ovum and have their own, bacteria­like DNA.) A full sequence of affected family members’ mitochondrial genome revealed 14 differences from standard sequences. Thirteen had been previously reported to have no impact. The 14th was new and was mapped to a gene for a transfer RNA, a molecule essential to building proteins. In fact, the gene is constant across animals, fungi, plants, and even bacteria.

Why it Matters: Against a noisy backdrop of studies showing how heart disease, depression, and other complex diseases can be attributed to small effects from many genes, Wilson and his colleagues’ research shows that a single gene can be tied to many disease-associated conditions. More importantly, the research pins responsibility for several diseases on mitochondria, whose function declines with age. Those seeking the fountain of youth, or just hoping to stave off the ravages of old age, may benefit from further studies of these vestiges of ancient bacteria.

Source: Wilson, F. H. et al. 2004. A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science 306: 1190-1194.

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