SCIENCE TRIBUNE Thursday, August 29, 2002, Chandigarh, India

DNA vaccines hold big promise
Rajeev Goel
O
NE of the greatest achievements of modern medicine is the generation of different vaccines that have saved lives of millions of people from hepatitis A&B, meningitis, measles, typhus, tetanus, rabies, rotavirus and other deadly infections. The vaccines have eradicated smallpox and equally encouraging is the predicted eradication of polio.

Remote-controlled rats
Shirish Joshi
N
EXT time you see a rat moving across your office or home, beware, it might not be as harmless as it seems. It could be a remote-controlled robo-rat working for an intelligence agency or Tehelka team, the people who created a stir some time back. The latest achievement in brain-machine interfaces — remote controlled rats — was developed by Dr Sanjiv Talwar and his colleagues, at the State University of New York with a view towards making artificial limbs that not only respond to a user’s commands, but also transmit back a sense of touch.

SCIENCE & TECHNOLOGY CROSSWORD

NEW PRODUCTS & DISCOVERIES

  • TO GET WARM, JUST BLOW
  • PHONES THAT READ YOUR LIPS
  • SIMULATIONS FOR SMALLPOX ATTACKS


Top






DNA vaccines hold big promise
Rajeev Goel

ONE of the greatest achievements of modern medicine is the generation of different vaccines that have saved lives of millions of people from hepatitis A&B, meningitis, measles, typhus, tetanus, rabies, rotavirus and other deadly infections. The vaccines have eradicated smallpox and equally encouraging is the predicted eradication of polio.

These have no doubt made an outstanding control over a number of diseases that caused significant mortality and morbidity. But still there remains a crying need for vaccines against others like malaria, tuberculosis, hepatitis C, herpes, AIDS etc.

The standard immunisation methods have failed to provide protective immunity against these. The alternative strategies are, therefore, needed to make vaccines for the diseases that have no effective vaccines available so far.

Mechanism of DNA vaccination
Mechanism of DNA vaccination

One of the most promising and recently developed vaccination strategy is the use of genetic material i.e. DNA to make genetic vaccines. In fact, genetic vaccines or DNA vaccines are an exciting outcome of recombinant DNA technology or genetic engineering. It is believed that these vaccines although still in the experimental stage of development, might one day prevent AIDS, malaria and other fatal infections.

The mechanism of action as well as merits of genetic vaccines could only be appreciated if we are familiar with the standard immunisation methods. The immunity to microorganisms or pathogens is achieved either by passive immunisation or active immunisation. The aim of the passive immunisation is to provide transient protection or alleviation of an existing diseased condition. The agents used for inducing passive immunisation include transfer of antibodies to an individual. The passive immunisation is routinely administered to individuals exposed to measles, tetanus, hepatitis, diphtheria, botulism, rabies, snakebites etc. It is also given to health care workers and travellers to provide immediate immunity.

The active immunisation is known as vaccination and its goal is to provide long lasting protective immunity. Vaccination or active immunisation is achieved by inoculating the microbial pathogens that are either killed (killed vaccines) or weakened (live attenuated vaccines) so that they themselves do not cause any disease or infection. The active immunisation or vaccination begun at about two moths of age and some of the prominent vaccines, are hepatitis B, poliovirus (OPV), measles, mumps and rubella (MMR), diphtheria, tetanus & pertussis (DPT) etc. The introduction and widespread use of various vaccines for childhood immunisation has drastically reduced the incidence of common childhood diseases like polio almost throughout the world.

But these vaccines do have their limitations and side-effects, though extremely rare. For example, killed vaccines may not have been properly killed. Weakened vaccines or vaccines prepared from weakened microorganisms may revert back to disease-causing forms. The vaccines during the process of manufacturing may get contaminated with undesirable proteins or pathogens. The individual may become allergic to such contaminated proteins. Further, live vaccines may cause full blown illness in people whose immune system is compromised as in AIDS, in cancer patients undergoing chemotherapy and elderly. Moreover, the individual vaccines like hepatitis B may be too expensive for the people they are designed for. Lastly, the most important is the failure of certain vaccines to shield against certain diseases.

The medical scientists have now observed that DNA vaccines prepared through recombinant DNA technology can address these problems posed by the traditional vaccines. It is now believed that DNA vaccines will preserve all the positive aspects of existing vaccines sans their risks. DNA or deoxyribonucleic acid vaccine consists of a circular piece of genetically engineered plasmid DNA carrying the genes specifying one or more proteins made by the selected pathogen (see figure). The plasmid DNA is originally derived from bacteria and is harmless. DNA vaccines are delivered either by injection or with needle-free devices like gene gun into the muscle cells of the recipient. The plasmid DNA is taken up by the cells, which then synthesise the protein corresponding to the gene of the pathogen. This protein then generates the immune response against that particular disease causing pathogen.

Experimental DNA vaccines for human viruses such as HIV, hepatitis B, herpes, influenza and plasmodium, the parasite responsible for malaria are currently being conducted in human trials at human research institutions. Preliminary reports state that useful immune response can be achieved DNA vaccines are even tried to treat cancers of prostate, skin and blood. Although cancer is not an infectious disease, many evidences indicate that activating the body’s immune response may help combat cancers.

DNA vaccines offer many advantages over the existing vaccines. They are easy to design and to produce in large quantities by use of recombinant DNA technology. Moreover, the same plasmid can be custom tailored to make a variety of proteins specific to different pathogens. This helps in making different DNA vaccines against different pathogens by using the same manufacturing technique. The DNA vaccines should therefore relatively be inexpensive. DNA vaccines can be distributed widely as they do not require any refrigeration for handling and storage. They are also easier to administer by using air gun or gene gun, thereby large population can be vaccinated without the need for massive quantities of needles and syringes. In addition, there is no fear of infection or full-blown illness by the use of DNA vaccines as these vaccines do not contain all the desired genes of the pathogen. Further, the plasmid can even be genetically engineered to carry genes specific for different variants (types) of the same pathogen like in case of HIV or influenza. The DNA vaccine prepared in such a way provides effective immunity against all variants at once. This is not possible by standard immunisation methods.

Results to date with DNA vaccines are highly promising but intensive research is still going on to know a) which doses of DNA vaccine are most effective; b) what will be the schedule of DNA vaccination; c) how long the immunity will last; d) how much will be the individual variations in their responses and above all one is yet to fully know the exact gene out of thousands in a given pathogen which should be selected to provide the maximum powerful immune response. Nonetheless, DNA vaccines are likely to be used for human immunisation within next few years once these queries are properly addressed.
Top

Remote-controlled rats
Shirish Joshi

NEXT time you see a rat moving across your office or home, beware, it might not be as harmless as it seems. It could be a remote-controlled robo-rat working for an intelligence agency or Tehelka team, the people who created a stir some time back.

The latest achievement in brain-machine interfaces — remote controlled rats — was developed by Dr Sanjiv Talwar and his colleagues, at the State University of New York with a view towards making artificial limbs that not only respond to a user’s commands, but also transmit back a sense of touch.

The scientists were able to make the rats run, turn, jump and climb where they wanted. The rats, each wired with three hair-fine electrical probes to their brains, could be directed through remote control by an operator typing commands on a computer up to 500 metres away. The animals were not only doing something, they were enjoying something.

They outfitted the rats with two probes to the brain that trigger sensations similar to what a rat would feel if touched at its right or left set of whiskers. A third probe touched the rat’s so-called medial forebrain bundle, or MFB — a section of the brain that relays a feeling of happiness or reward.

Wires from the probes ran into a small box that each rat carried on its back. It contained a tiny antenna and remote-controlled stimulator. When activated, the MFB probe encouraged the rats to keep running, even if steep climbs or obstacles or brightly-lit areas lay ahead.

The other wires directed the rats to turn right or left. The rats responded consistently to the signals after brief training in a maze. Then the rats followed the commands outside while in an open field.

However, this is not the first time scientists have electronically manipulated the brains of animals.

In the 1960s, Yale physiologist Dr Jose Delgado proved that he could influence the mood and actions of animals through remote control. In one famous demonstration, Dr Delgado stood, unarmed, in front of a charging bull.

As the bull bore down on him, he flicked a switch on a small radio transmitter that sent charges to electrodes implanted inside the bull’s brain and the animal immediately braked to a halt and meekly walked away.

Dr Delgado also experimented with monkeys and cats and generated horror when he suggested the technology could be used to limit obsessive and criminal behaviour in human societies.

Researchers at Duke University wired monkey brains to control robotic arms. And researchers at the University School of Medicine in Philadelphia demonstrated that signals from cells in a rat’s brains could be used to control a device without the rats carrying out a physical action themselves.

Dr Talwar suggests the rats might also be used as scouts for search and rescue teams looking for survivors amid rubble or for sniffing out hidden landmines, and even climb trees, and for mapping of underground areas.

By installing the global positioning systems (GPS) and possibly tiny video cameras on their backs, the rodents could offer rescue workers with living, robotic guides to find victims buried under rubble.

He points out that rats have the ability to travel adeptly over rough terrain, therefore they might be more easily deployed in chaotic environments.

If equipped with sensors to detect explosives — or a device to read the animal’s olfactory response — the rats might also help in finding bombs or landmines. The rats could also travel up trees and through rough terrain with much more skill than fully automated robots.

According to Dr Talwar, the rat can serve both as a robot and as a biological sensor at the same time. This is the biggest advantage.

However, as expected, the concept has not been well received by animal rights groups. Dr Talwar is well aware that his remote-controlled rats pose ethical questions that will need to be answered.
Top

SCIENCE & TECHNOLOGY CROSSWORD

Clues

Across:

1. Instrument to measure the thickness of paint over a surface.

6. An inert gas used in electric tubes.

7. Created on the desktop for quick opening of a programme.

9. Monumental ancient structure of stone with polygonal or square base.

11. Doctor’s language for one pill a day.

12. A substance on whose surface the absorption i.e. higher concentration of molecules takes place.

14. Symbol for Neon gas.

15. A tree with silver-gray bank and pinnate foliage.

17. Occurring in a machine causing its stoppage.

20. Flat representation of a building or of earth’s surface.

21. Add effects to a film or a broadcast.

23. Thin wedge used in machinery to make parts fit together.

24. Swelling of the ear.

27. Plant covered with stinging hairs.

28. These rays produce intense ionization in gases through which they pass.

Down:

1. Scope for this must be kept to avoid cracks in structures.

2. This jar has a parallel plate capacitor made up of two cylindrical tin foil coatings.

3. One of the best scientific research centres of the world, now working on movements inside the volcanoes. (abbr.)

4. Rise and fall of sea occurring at every 12 hour intervals.

5. Parts of plant attached to Earth for nourishment from soil.

8. Symbol for Semi-metal Neodymium.

10. International organization for standardisation of weights and measures.

13. A mixture of hydrocarbons obtained from paraffin oil, coal tar etc.

16. Organic constituent of soil.

18. Almost horizontal entrance to a mine.

19. …..percha, a naturally occurring polymer used as a rubber additive.

22. Bitter fluid secreted by liver to aid digestion.

25. Best known anti-knocking agent added to gasoline.

26. A programme of Govt. of India to provide agro based self employment to needy women.

Solution to last week’s Crossword:


Top

Home

NEW PRODUCTS & DISCOVERIES

TO GET WARM, JUST BLOW

All those layers making you feel a little, well, wrapped too tight? Gore’s Airvantage vest provides the warmth without any of the mummification.

The vest takes advantage of the inherent insulating abilities of air (the secret behind double-pane windows).

When you’re getting chilly, just blow into the chest-pocket tube. This fills a labyrinth of inner cavities, raising the vest’s insulating ability from spring day to autumn night.

PHONES THAT READ YOUR LIPS

Scientists in Japan are developing new technology for mobile phones that should allow the electronic devices to read lips.

According to a report in the latest New Scientist magazine, Japanese mobile giant NTT DoCoMo is working on technology that will let mobile phones read lips so users will not have to shout into the mouthpieces of their handsets. The technology could also be used to help people who have lost their voice to use mobiles.

Another possible use of the technology would be its ability to convert movements of the mouth into text to be sent as an SMS or e-mail.

The magazine says that the company’s engineers have developed a prototype device which can read vowels and now they are focusing on consonants. Within the next five years the company hopes to launch a working model.

Phones equipped with the technology should be able to convert minute electrical signals generated by the muscles in the mouth into a computer synthesised voice so that users would only need to mouth what they want to say and a synthesised voice would speak to a listener.

The magazine says that the system in place now, which is only able to detect vowels, has an acceptable error rate, but consonants are much harder to detect. The engineers are thought to be considering the use of tiny digital cameras to aid in the lip-reading technology.

One of the benefits of such technology, according to NTT, would be the effect it would have on already noisy locations, or places where it may be considered rude to chat on a phone such as a quiet restaurant. With the technology in place, users could have discrete conversations over their phone while also respecting generally accepted mobile phone etiquette.

SIMULATIONS FOR SMALLPOX ATTACKS

Imaginative minds can conjure horribly apocalyptic consequences from a smallpox attack.

Here is a disease that kills 30 per cent of those it infects and leaves survivors permanently scarred. After plaguing humanity for centuries, it was finally eradicated three decades ago so that no one today has any built-up immunity to it. The smallpox vaccinations some people had as children would no longer be effective. Unchecked, smallpox has the potential to sweep through the population like the plagues of medieval Europe.

But with the help of computers, many researchers are concluding that a smallpox attack by terrorists need not produce an uncontrollable public health crisis. Computer simulations show that the proper combination of post-attack vaccination, quarantine and other public health measures could stop smallpox in its tracks. AP

Top