SCIENCE & TECHNOLOGY

A major breakthrough
Silencing the genes
Dr Rajeev Goel

G
ene
therapy is one of the most radical notions ever put forward in medicine. The medical scientists who used gene therapy to cure mainly the genetic disorders so far are now envisaging that almost every disease will have gene therapy as one of its treatment by next decade or so.

Mouse embryo from eggs
J
apanese
scientists have succeeded in cloning mouse embryos from unfertilised eggs, a breakthrough that could help resolve the passionate ethical debate about stem cell research.

Eat fish, beat malaria
A
nutritious fish eaten in Kenya could be used as a weapon against malaria, according to a study of three fish ponds where the species nearly wiped out mosquitoes that transmit the deadly disease.

TRENDS
Fossil tells of evolution

An ancient skull and upper jawbone from two early branches of the human family tree — Homo erectus and Homo habilis — suggest the early human ancestors may have lived close together for half a million years, researchers said on Wednesday.

  • No drunk astronauts

  • Microbes come back to life

THIS UNIVERSE
Prof Yash Pal

Prof Yash Pal

Prof Yash Pal

 


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A major breakthrough
Silencing the genes
Dr Rajeev Goel

Gene therapy is one of the most radical notions ever put forward in medicine. The medical scientists who used gene therapy to cure mainly the genetic disorders so far are now envisaging that almost every disease will have gene therapy as one of its treatment by next decade or so.

Gene therapy till now involved replacing defective genes with normal genes or adding a few normal genes to diseased cells to enable them to form functionally active proteins. The proteins in turn either correct the deficiencies that lead to disorders or enhance body resistance to diseases.

Although conceptually straightforward, the replacement of defective genes or adding normal genes is technically quite challenging and only a very small segment of patients are treatable by the current existing techniques of gene therapy. However, during the course of research, the biomedical researchers discovered that “silencing or switching off” a defective gene to render it incapable to cause disease can be a good alternative to replacing or adding the normal genes.

The silencing of the defective gene is achieved by injecting in diseased cells, the short pieces of double stranded ribonucleic acid (RNA) which is a close relative of our hereditary substance – the DNA. In technical parlance, such a method of gene silencing by using RNA is called RNA interference (RNAi). Keeping in view the high potentials of RNAi based gene silencing, it was awarded the Nobel Prize in Physiology or Medicine for the year 2006.

The genetic information is stored in our cells in double stranded DNA — the deoxyribonucleic acid. The stored genetic information by a process of gene expression is copied into a single stranded messenger RNA (mRNA). The mRNA acts as a “middle man” in the sense that it carries the genetic information contained in DNA to be decoded into functional proteins. The proteins in turn run various metabolic functions & repair in the body.

In case there exists a defective DNA, it would, therefore, be copied into a defective messenger RNA that would form an abnormal protein which would disrupt the normal metabolism of the body. It is by the RNA interference (RNAi) based gene silencing technology that such a defective DNA or a gene can be switched off. RNAi uses bits of therapeutic RNA {also called short interfering double stranded RNA (siRNA)} which binds to and destroys/cleaves the messenger RNA of the defective gene when introduced into the diseased cells. This ultimately shuts down the formation of a defective protein & save the cells from its deleterious effects (see diagram).

Applications

One can target and knock down virtually any diseased gene or set of genes by making use of RNA interference technology. It is being tried to switch off viral genes coding for hepatitis B or C, HIV and the cancer causing genes.

It is presumed that gene silencing by RNAi may provide permanent cure for certain neurological disorders like Alzheimer’s & Huntington’s diseases, spinocerebellar ataxias, amyotrophic lateral sclerosis (ALS) etc. which otherwise is not possible due to the existence of blood brain barrier. The barrier prevents the passage of most of the proteins and pharmaceutical molecules in the blood from reaching the highly fragile and protective environment of the neurons of the brain which can be overcome by targeting gene silencing of the diseased gene in the brain of an affected individual.

Limitations

While RNAi looks quite promising, it has mainly been tried either in test tubes or animal models. However, a few clinical trials are underway but translating this technology to human beings has been a big hurdle due to certain ill effects of RNAi therapy observed in animal studies.

Moreover, the researchers are still to find out whether it should be started before or after the patient starts showing the symptoms of the disease especially in case of neurological disorders. The dosage and frequency of RNAi therapy required by a patient and its long-term efficacy is also not known. In addition, the safe and effective delivery methods (presently modified viruses are used) to carry the interfering RNA into the diseased cells are to be explored. A lot of research & clinical trials are, therefore, required to address these unanswered questions before the RNAi gene therapy can be safely used in human beings. Till then, good luck to medical researchers!
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Mouse embryo from eggs

Japanese scientists have succeeded in cloning mouse embryos from unfertilised eggs, a breakthrough that could help resolve the passionate ethical debate about stem cell research.

Advocates say research involving embryonic stem cells — cells that can develop into various organs or nerves — can save lives by finding cures for diseases such as cancer and diabetes.

But the research has provoked a furore among religious conservatives, who argue that it destroys a human life — albeit one at its earlier stage of development.

President George W. Bush has banned all federal funding for stem cell studies in the United States, the world biggest research hub.

One proposed alternative has been to use unfertilised human eggs, but this presents the major obstacle of trying to persuade healthy women to undergo the painful process of donating eggs.

A Japanese team said it has found a potential future solution — it performed in vitro fertilisation with mice and found that egg cells that failed to be fertilised could be used to make cloned embryonic stem cells.

The process could be put to use among human eggs that would have gone to waste during in vitro fertilisation.

“If we can use egg cells that would have been dumped, then the problem of finding donors will be solved,” said Teruhiko Wakayama, who led the study at the Japanese government-backed Riken research foundation.

“Before our findings, it was believed that only fresh eggs could be used. But if incompetent eggs can be cloned, then scientists could be given eggs that failed to be fertilised and would have been abandoned in fertility clinics,” Wakayama said.

Japan, the largest spender on research after the United States, has few restrictions on stem cell research. In Washington, Democratic lawmakers have been pushing to lift restrictions on stem cell research since they took control of Congress in January from Bush’s largely anti-abortion Republicans. — AFP
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Eat fish, beat malaria

A nutritious fish eaten in Kenya could be used as a weapon against malaria, according to a study of three fish ponds where the species nearly wiped out mosquitoes that transmit the deadly disease.

Researchers have long known that the Nile tilapia feeds on mosquito larvae but the study was the first to test its potential to fight the disease in the field, said Francois Omlin, a researcher at the International Centre of Insect Physiology and Ecology in Nairobi.

“A fish in the field may act differently than a fish in an aquarium and it was important to test how effective it could be,” Omlin, who led the study, said. “The tilapia species was never tested in the field for its ability to eat mosquito larvae.” Malaria, caused by a parasite carried by mosquitoes, kills more than 1 million people a year worldwide and makes 300 million seriously ill. —Reuters
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TRENDS

Fossil tells of evolution

An ancient skull and upper jawbone from two early branches of the human family tree — Homo erectus and Homo habilis — suggest the early human ancestors may have lived close together for half a million years, researchers said on Wednesday.

The fossils, discovered in eastern Africa, challenge the understanding that humans evolved one after another like a line of dominoes, from ancient Homo habilis to Homo erectus and eventually to Homo sapiens, or modern people. — Reuters

No drunk astronauts

NASA has reviewed 10 years of space flights and found no evidence to back up allegations that astronauts boarded a space shuttle and a Russian Soyuz spacecraft drunk, the U.S. space agency’s boss said on Wednesday. The agency was investigating every flight involving shuttles, the Soyuz and the T-38 trainer jets flown by astronauts, NASA Administrator Michael Griffin told reporters.

“Right now, we’ve gone back 10 years and we can’t even find where it would be a possibility there was crew under the influence on either a Soyuz or a shuttle,” he said. — Reuters

Microbes come back to life

Microorganisms locked in Antarctic ice for 100,000 years and more came to life and resumed growing when given warmth and nutrients in a laboratory.

Researchers led by Kay Bidle of Rutgers University tested five samples of ice ranging in age from 100,000 years to 8 million years.

“We knew that microorganisms were really hardy,” Bidle, an assistant professor of marine and coastal sciences, said in a telephone interview. — AP
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THIS UNIVERSE
Prof Yash Pal

A person who sees others yawning also begins to yawn. Why?

This is a truth about which I cannot give a very cogent and scientific explanation. What is more, I have not seen it in anything I have read. I do not know why we yawn. I can only guess. When we are tired and sleepy, most of us yawn. Do we have a need for gulping in more oxygen? Perhaps.

Do we want to send a signal to friends and relatives around us that we have had enough of their company and we must take leave and go in for a shuteye? Perhaps. I do know that when we are listening to a particularly boring speech we become drowsy and begin to yawn? This particular yawn is especially contagious. This usually happens in late afternoon.

The fact that it happens is indisputable. But there are lectures and speeches that wake us up and all yawing disappears. This shows that the origin of yawning is not only physiological. Intellectual and emotional engagement — or disengagement — also makes a difference.

The contagious property of yawning is understandable if the people who are simultaneously affected are together late in the day and listening to the same boring speaker. Perhaps disengagement of some in the audience, when noticed, leads to a similar disengagement of others. I have found that when I notice just one shining pair of eyes focused on the speaker, I also become more attentive.

Besides physiology, social psychology is simultaneously at play. In spite of all these observations I still cannot tell you why yawning should be such a widespread symptom when some tiredness is combined with boredom.

Only the young have the courage to pull out a novel or a short story book to overcome the boredom. Most others feel socially obligated to simulate attention with their eyes open and staring at the speaker — a stance not very conducive to an engaged presence at the event.

Having said all this I might also point to another category of yawning that is perhaps better understood. Many of get up in the morning after a restful sleep and shake away the last dregs of drowsiness by stretching our arms and a big yawn.

This tendency perhaps helps to expand our lungs and fills them up with a large mouthful of air. I do not think this yawn is that contagious, partly because we seldom wake up at the same place at the same moment.

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