by Dr. Atta-ur-Rahman
Prof. Dr. Atta-ur-Rahman is the most decorated scientist of Pakistan having won four civil awards by the Government of Pakistan

Gene Therapy - for Colour Blindness

The unraveling of the structure of the human genome has opened up opportunities for addressing genetic defects. About 1 in 12 men and 1 in 230 women suffer from some form of colour blindness or related defects. These are usually caused by mutations in genes which result in inactivation of the light absorbing pigments present in the eye retina. If the red photopigment is absent, it results in red and green objects appearing as different shades of grey. This defect is also found in some types of monkeys. Jay and Maureen Neitz, a husband and wife research team at the Eye Institute of the University of Washington, have discovered that it is possible to cure this defect employing gene therapy. A virus containing the defect-free gene was injected into adult color blind monkeys. The monkeys were trained to identify coloured spots on computer screens, being rewarded by squirts of fruit juice each time they touched the screen at the correct place. Initially the colour blind monkeys could only identify yellow and blue spots, but could not recognize red and green spots properly. Five months after the gene therapy, the monkeys suddenly became capable of identifying the red and green spots (Nature, p 695, vol.461, 8 Oct.2009).

Before long the treatment is likely to become available for humans. 

Gene Therapy - for Alzheimer’s  Disease

Certain diseases are caused by defective genes. Gene therapy involves insertion of genes, or alteration/ replacement of genes in a person’s cells and biological tissues to cure the disease. It is still in its infancy and limited successes have been achieved employing it.

Now scientists at the Feinstein Institute for Medical Research in Manhasset, New York have found that it is possible to improve the condition of patients suffering from Parkinson’s disease by using gene therapy. Parkinson’s disease is a neurodegenerative disorder that causes tremors, rigidity of muscles, sluggish movements and impairment of balance. The condition is caused due to the lack of a chemical substance in the brain (GABA). The scientists introduced a virus into the brains of such patients that contained a gene that was able to increase the levels of GABA. This led to a marked improvement in the condition of such patients in clinical trials.

Scientists at Imperial College, London’s Department of Gene Therapy, led by Gene Therapy Professor Nicholas Mazarakis have also been making significant progress in using gene therapy to treat various motor neurone disorders. This is an exciting horizon in medicine.

Design Your Babies

On March 3 last year the front page story in New York Daily News related to a service being offered by an organization, Fertility Institutes, which would allow parents to choose the colour of their baby’s hair, eyes and skin. Fear of negative public reaction forced the institute to cancel the project, but this may be only temporary as the technology is here. It involves testing the embryos prior to fertilization in the womb, and is known as preimplantation genetic diagnosis (PGD).It has already allowed thousands of parents to prevent genetic diseases being passed on to their children. 

A menu of traits can now be offered after examining the genetic structure of embryos and the horrible prospect of breeding humans with special features, such as height, fighting characteristics or intelligence may be around the corner. Indeed in certain defense establishments in advanced countries, this may even be happening today secretly.

Battle against HIV - Winning at Last?

AIDS continues to be a big killer, particularly in Africa. In 2007,  about 2 million people died and another 2.7 million people were infected by this devastating virus. However a cure may be around the corner and there is renewed hope for AIDS patients - using gene therapy! A man in Germany suffering both from leukemia and AIDS was cured after being given a bone marrow transplant which replaced the patient’s immune cells. The spectacular discovery made by Gero Hutter was published in The New England Journal of Medicine (vol.360, p 692). However bone marrow transplant is not an option because bone marrow donors are rare and the treatment would be cumbersome and expensive. A US company Sangamo Biosciences is however developing a gene therapy based cure which would emulate the effect of the bone marrow transplant. If successful, just one shot of gene therapy could completely eradicate this deadly virus. Presently the best approach used against HIV is the use of antiretroviral therapy (ART). However these drugs have to be used all one’s life, and they are expensive. 

Is a Flu Pandemic Coming?

There is a growing concern among many scientists that a major flu epidemic which can take millions of lives may be inevitable. Scientists are worried that history may repeat itself. In the 1918 Spanish flu pandemic, about a billion people were infected, and some 50 to 100 million people died - an astonishingly high figure. More than 200,000 people died in USA in just one month. The swine flu virus which originated in Mexico has spread rapidly across the world. The Mexican flu virus is very different in its structure as compared to the existing flu viruses, which means that humans have not developed any natural immunity to it. If it evolves into a more deadly variety, tens of millions could die again.

Pharmaceutical companies are unwilling to risk producing large quantities of vaccines with no guarantee of efficacy if the virus continues to mutate, or of sales if the pandemic does not materialise. If the flu turns into a nasty killer, most countries will be left at its mercy due to non-availability of vaccines. The 1918 flu epidemic started in a mild form in spring but had mutated to a lethal killer by that autumn. It could be even more devastating now due to far greater number of travelers across the globe. What is alarming is that the world is not prepared.

Exciting Advances Against Flu

Influenza (flu) attacks several million people each year, causing 250,000 to 500,000 deaths annually. In pandemic years, the death toll can rise to millions. Flu is caused by certain types of RNA viruses that attack mammals and birds. In advanced countries it is quite common for the elderly to get themselves vaccinated against it, so that they are completely or partially protected. 

However, the virus is quite a scam artist, since it uses ‘smoke and mirrors’ to deceive the attacking antibody or vaccine. It evolves by rapidly changing the structure of the protein coat that it wears on its surface so that vaccines effective against it in one year lose their efficacy in a subsequent year as it has changed its coat (surface protein) by which it was being recognised. The problem is complicated by the fact that there are sixteen different types of coats (surface proteins, proteins Hemagglutinin (HA)) that it can wear, so that any vaccine effective against one of these viruses will be ineffective against another. 

There has, therefore, been a search by researchers to discover a region of that surface protein coat which does not change. The protein is shaped like a mushroom and at the stalk of this mushroom-shaped protein such a region has now been discovered. 

Scientists at Scripps Research Institute in La Jolla, California, collaborated with Peter Palese and colleagues at Mount Sinai Medical School in New York to develop a vaccine which was effective against all flu viruses that attack human beings. Experiments carried out on mice infected with these viruses showed that the vaccines developed reduced the severity of the flu attack against all the virus types, thereby holding out hope that an effective vaccine against all types of flu viruses may soon become available. An Israeli firm, Biondvax, and the American firm, Dynavax, are in the process of developing the vaccines commercially. 

Detecting Swine Flu

A major pandemic which could kill tens of millions may be imminent, and some airports are preparing themselves to detect incoming flu patients, using the latest technologies. CAPSCA (the Cooperative Arrangement for the Prevention of Communicable diseases by Air travel) is involved in helping airports in this respect. Infra-red cameras have already been installed at some airports to detect passengers with fever. The first swine flu patient in Turkey was detected with this technique. However the procedure is imperfect since swine flu is infectious even a day before the patient develops a fever. Such patients can escape undetected through these surveillance devices. A cough detector has also been developed which can distinguish the difference between a person simply clearing his throat from the cough of a sick person. Such devices could be built into phones so that health authorities are alerted when a sick person is making a call. Recently the Japanese government has initiated a GPS based 2,000 person trial which will alert the cell phone users if their GPS history shows that they may have been exposed to infection.

Swine Flu is Coming

Next  winter may pose a huge challenge for mankind - swine flu is intensifying and the pandemic becomes more serious with each passing day. It is also replacing the normal strains of seasonal flu, thereby creating new risks. The Spanish pandemic flu in 1918 was the most devastating in human history, leading to some 50 million deaths. The Asian avian influenza, which originated in China from ducks in 1956, caused over 2 million deaths. The Hong Kong flu in 1968 killed about a million people world-wide and affected some 500,000 people in Hong Kong alone. 

In the US, more than 98% of flu cases in June this year were due to swine flu. In Victoria (Australia) 99% of the reported flu cases were also due to H1N1 swine flu. Similarly in Chile and Argentina more than 98% of flu cases are due to H1N1 swine flu. There are ominous signs that the virus may be beginning to mutate to a more lethal and resistant form. Some cases of swine flu resistant to the anti-viral drug Tamiflu have also been reported. In Pakistan an increasing number of cases of swine flu  have been reported, and a number of deaths attributed to it. It is important to have access to vaccines - these are not available in Pakistan presently, specially for the susceptible populations.

Nanoparticles for Detecting Tuberculosis

The identification of tuberculosis, which involves growing large colonies of the bacteria, can take a couple of weeks. Now a test has been developed using magnetic nanoparticles which can identify the disease causing bacteria within 30 minutes! The nanoparticles are coated with antibodies that can bind to the TB-causing bacteria and detected by a magnetic scanner. The work was recently reported by scientists at the Harvard Medical School and is expected to greatly facilitate early detection of this disease (Angewandte Chemie, DOI:10.1002/anie.200901791).    

Diabetes: Bacteria to the Rescue

John March and colleagues at Cornell University have engineered a strain of gut microbes (non-pathogenic E.coli) which secrete a protein (GLP-1) that triggers the release of insulin by human intestinal cells in the lab in response to glucose. When the bacteria were administered to diabetic mice, the sugar levels of such mice were restored to normal levels. It is hoped that the approach can be used to develop a yoghurt drink containing such engineered bacteria for treating diabetic patients. An advantage of the approach would be that since the bacteria would secrete just the required amount of the protein in the patient, the right amount of insulin will be produced and the constant need of self-monitoring of sugar levels would be eliminated.

Curing infections - with Magnetism

An exciting new development on the horizon uses iron oxide beads coated with antibodies to seek out and trap bacteria or fungi causing infections. The beads are very fine, having the thickness one-hundredth of that of a human hair, and they are injected into the blood stream of patients. A dialysis-like machine employs an electromagnet to pull out the beads, along with the disease causing bacteria or fungi stuck to the antibodies on the beads, from the blood into a saline solution. About 80% of the disease-causing agents are thus removed, making it much easier to tackle the rest with drugs. The treatment is thought to be particularly useful when wounds become septic, and organ failures can take place before the drugs have a chance to act. A large number of sepsis related deaths occur each year. Animal trials taking place currently under the supervision of Prof. Don Ingber at the Harvard Medical School and Children’s Hospital will be followed by human trials. The technique also has the potential of removing cancer cells or harvesting stem cells.

Healing Wounds - by Printing

Ink jet printers are commonly used for printing documents. An astounding break through has recently been made by doctors at the Wake Forest Institute of Regenerative Medicine in USA in which they have used a device that resembles an ink jet printer but it can be used for spraying new skin cells on to burn wounds, thereby dramatically shortening the healing time. This method results in rapid healing and it could eventually replace the need of having skin grafts.

The device resembles a colour ink jet printer, comprising a tank that contains skin cells, stem cells and nutrients. These are sprayed by a computer controlled nozzle directly on the burnt area. In animal experiments, flesh wounds in mice were fully healed within 2 weeks as compared to 5 weeks taken by skin graft procedure, showed less scarring and better hair regeneration. The technology will be initially employed by the US army to “print-shut” bullet wounds and blast damage. 

Malaria - A Vaccine At last

Each year some 300-350 million cases of malaria are reported, and about 3 million persons die, mostly children in sub-Saharan Africa. Now there is hope. A vaccine has been developed by Glaxo-Smith Kline that reduced infection by 65% in children during small scale clinical trials in Kenya and Tanzania. Now large scale trials are being carried out at on 16,000 patients in 11 hospitals in Kenya, Burkina-Faso, Malawi and Tanzania. If the trials are successful, the vaccine should be submitted for regulatory approval next year.

Anti-viral Drugs - for Future Viral Diseases

A major challenge for scientists is to cope with viruses that may suddenly emerge, as happened with HIV, SARS, Ebola and H1N1 which were unknown in human history. As we do not know which viruses may evolve in the years ahead, development and large scale manufacture of vaccines to cope with such a pandemic poses a huge problem. Michael Godblatt, who was leading the biodefense programme at DARPA (a research arm of the Pentagon) began to work on a new generation of anti-viral drugs, which he hoped would not only be effective against all presently known viruses but also be effective against any viruses that may evolve in the future. This seemed to be too good to be true. However after moving to a biotech company, Functional Genetics, in Gaithersburgh, Maryland, his team has developed some drugs which have shown promise in clinical trials. His work relies on the fact that viruses are utterly helpless without the hosts. It is by deceiving the host cells to make multiple copies that viruses multiply. What if one could identify and block the proteins in the host which are essential for the multiplication process? This would prevent the killing of healthy cells as well as prevent virus multiplication. They targeted a particular protein (TSG 101) in the host which the viruses need to break-out from the host cells. One drug (FGI-104) was found to be active against a large number of viruses (HIV, hepatitis C, Ebola) and may represent a new chapter in anti-viral drug development. A number of other groups have developed similar approaches.

It remains to be seen if viruses can evolve in a manner that can circumvent this new threat against them. The battle goes on! 

Killing Viruses - with Ceramics

A novel ceramic coating has been developed by a UK based company, Intrinsiq Materials in the UK, based on the researches of John Oxford and colleagues at Queen Mary, University of London. It was found that nanoparticles made from silica and metal carbide ceramics could kill 99.9% of viruses within an hour. Applications for which this material could be used are face masks, air filters, cash machines, trolley handles in super markets and even bank notes which may be infected due to public handling.

Relieving Allergies - with Parasitic Worms

There is growing evidence that infections with certain parasitic worms can have beneficial effects for patients suffering from certain types of allergies. It has been shown in Ethiopia that the severity of asthma can be reduced if patients are exposed to hook worms. In Brazil, patients suffering from asthma could get relief if they were infected with a flatworm responsible for the tropical disease schistosomiasis (Lancet, vol 358, p1493). In Taiwan it was shown that patients infected with a pinworm were much less likely to suffer from hay fever (Clinical Experimental Allergy, vol.32, p1029). These and other results indicate that the immune system is triggering positive responses to infection by different types of worms. Scientists at Imperial College London have also recently found protective effects of parasitic worms against pneumonia caused by influenza.

Such helminthic therapies may reveal exciting underlying factors in the future. 

Electronic Pills

Almost all drugs have some side effects, and tend to affect other organs besides the ones that are being targeted. This limits the dosage of the drugs being administered. Clearly if there was some way to control their release so that they would affect mainly the diseased organ, it would be very useful. 

A new approach being developed is that of an electronically controlled pill ("iPill") that will reach the site of the infection, release the drug directly on the infected area, and then pass out of the body without causing harm. The approach is particularly suitable in diseases of the gastro-intestinal track such as colitis, inflammation and colon cancer. The pill is controlled by a microprocessor with which the doctors can monitor its exact location, pH and the time of its release. A small radio transmitter embedded in the pill relays the data to an external computer with the doctor, allowing the monitoring of the position of the pill and release of the drug at the desired site. The pill contains a tiny motor that drives a piston to dispense the drug through small holes in the pill. The iPill, which has been developed by Philips, is likely to become available commercially soon. 

Robo Nurses

She is tall, caring with gentle sensitive fingers and a soft affectionate voice watching over you day and night - but she is not human but a robot!  Her fingers can delicately grip a drinking straw but her arms are strong enough to lift you up like a small child and carry you as if you were a baby. Developed by researchers at Waseda University in Tokyo, Japan, and known as “TwendyOne”, the robo nurse can be particularly useful for elderly patients requiring constant care. It can readily accept commands such as to get medicine, refreshments or otherwise help the patient. 

Converting Bacteria to Robots

Can you command bacteria to perform specific tasks, just like robots? Now you can! Prof. Sylvain Martel and colleagues at the NanoRobotics Laboratory of Ecole Polytechnique de Montreal, Canada have used a magnetic device to control and command bacteria to build a small pyramid! Certain bacteria (magnetotactic bacteria) have built-in natural compasses (“magnetosomes”) that forces them to follow the pull of a magnetic field. These bacteria were induced by scientists using external magnetic fields to form a giant computer controlled swarm of about 5,000 bacteria which was then “persuaded” to build a small pyramid from tiny epoxy bricks within 15 minutes. In another experiment, the bacterial swarm was forced to travel through certain blood vessels. The scientists are now planning to use these tiny work horses to act as engines that will propel larger nanorobots carrying specific drugs to the site of infections! Bacteria could also be used for detecting other disease causing microbes, as well as to operate micro-factories for performing genetic and pharmacological tests. With “synthetic life” having been developed recently by Craig Venter and colleagues in USA.

Computer designed DNA can now be inserted into bacteria which can reproduce themselves with the new genetic information to meet specific human needs for drugs, pesticides, fuel and energy. No unions, no protests, no hassle - millions of tiny workers at work using tiny magnetic fields as the drivers.

(To be continued)