Sunday, July 1, 2007

The Elixir of Life?

Pregnant women in UK were warned in June 2006 not to use companies that offer to store stem cells from their babies' umbilical cords as the companies' claims of providing the ultimate insurance against future disease are "extremely speculative". The Royal College of Obstetricians and Gynecologists (RCOG) has issued an updated version of its Scientific Opinion Paper on Umbilical Cord Blood Banking. The report finds that there is little evidence to recommend the practice whereby private companies collect and store umbilical cord blood for up to twenty years - at a charge of up to £1500 - for possible future use. The National Health Service (NHS) currently collects cord blood from selected centers in the UK, where women are approached during the maternity period and offered the opportunity to donate. Essentially, their stance remains unchanged from the one taken in their previous opinion paper published in 2001. The RCOG stands firm in its decision not to support commercial storage where no history of medical illness exists, but continues to back both public donation to banks such as the NHS Cord Blood Bank for non-directed use and directed donations for at-risk families.

Stem cells from umbilical cord blood (UCB) have been used since the first successful transplant in 1988 on Matthew Farrow, a five-year-old boy who suffered from Fanconi's Anemia. Medical experts carried out the procedure at a hospital in Paris using the stem cells harvested from the cord blood of his newborn sister, Alison. This was to become the first of over 6,000 UCB transplants worldwide, treating disorders such as thalassemia, immunodeficiency, inherited metabolic diseases, aplastic anemia and acute leukemia. Today, Matthew remains durably grafted and living proof that UCB has enormous future potential.

Cord blood advocates are keen to point out the benefits of using UCB for transplant purposes as an alternative to the traditional method of bone marrow. Unlike its bone marrow counterpart, UCB stem cells need not be an exact match and are less likely to be rejected by the recipient. Cord blood is a readily available resource, collected at the moment of delivery without pain or relative risk to mother and baby. Furthermore, stem cells collected from this routinely discarded waste product fail to raise the same moral, social and religious objections associated with the procurement of stem cells from aborted fetuses and embryos created via assisted reproductive technology. So, what reasons are being given for ignoring a resource with such great potential?

Within the public sector, the logistics of collection from multiple hospitals and subsequent cost implications involved in collection and storage are obvious reasons given against routine collection, which would inevitably draw heavily on an already cash-starved public health services model. With regard to the private sector, many legal and ethical issues are raised. In spite of its potential, the RCOG purport that there remains insufficient evidence to recommend UCB collection in low-risk families. Expectant families are targeted by the use of emotive advertising literature in maternity clinics and the Internet. Critics of commercial banking argue that the costs of this service, which fall in the region of £1,200 for a 15-20 year storage term, are out of proportion in terms of the odds associated with their potential future use, currently estimated at between 1 in 20,000 and 1 in 2,700 for personal use.

Furthermore, personal banking may not be deemed necessary for certain conditions as alternative resources may be available from UK and international public cord blood banks and bone marrow registries. Critics also argue that personally banked UCB may contain disorders already present in the patient at birth, but as yet undetected, and the low number of cells within a unit means they may only be used at present for transplants in children and young adults. Concerns over storage conditions and longevity of the cells are also raised.

Although opinion remains divided over the need for parents to privately bank their baby's cord blood, those on either side of the debate agree on one thing - stem cells are the future - and, in particular, UCB stem cells show great promise.

Cord blood stem cells have been useful in the treatment of cancers such as leukemia. The NHS public bank collects 1700 to 2000 samples each year, which may be accessed by those in need. Cord blood storage is also offered to families affected by specific genetic disorders that may be treatable with a transplant, for example Fanconi anemia. Critics say that private companies play on parent’s fears, with the offer of future speculative treatments for many conditions not currently treatable with cord blood. Some promote their service to parents through leaflets provided in GP clinics and antenatal clinics.
Professor Peter Braude, head of the Department of Women's Health at King's College London and chair of the RCOG expert group commented, 'The likelihood of use is extremely small and some of the uses are extremely speculative'. Professor Braude went on to say that, 'Most people are unaware there is an NHS cord blood bank and most transplants are done with bone marrow'.

The major use for cord blood stem cells has been in the treatment of cancers such as leukemia in children. But some companies claim the stem cells may also be used in the future to treat conditions such as Parkinson's disease.

MARKETING PHRASES
'Unimaginable possibilities'
'A once in a lifetime opportunity'
'Like freezing a spare immune system'
Slogans used in promotional material by companies offering cord blood storage

The Royal College of Obstetricians and Gynecologists said there was "insufficient evidence" to recommend the practice for families at low risk of passing on blood diseases such as leukemia or genetic disorders. Those who believed they were obtaining "the elixir of life" for their child should realize that claims that stem cells can produce future cures for Alzheimer's, diabetes, and ovarian cancer are "in the realm of speculation".

"The ability to use it for diabetes or Parkinson's is like insuring against aircraft crashes," said Peter Braude, chairman of the college's scientific advisory committee. The warning came as the college issued fresh guidelines for obstetricians and midwives concerned about how to deal with an escalating interest in the storage of umbilical cord stem cells. The demand for private cord blood banks - such as the UK Cord Blood Bank, Smart Cells and Future Health - has grown in the past year with about 11,000 British couples reported to have paid around £1,500 to store the blood for 20 years. The footballer Thierry Henry and the dancer Darcey Bussell are among the celebrities who have paid for the service. The college said collecting stem cells for families at risk of genetic disorders, or from women donating altruistically, was acceptable but that this should be done through the NHS.

We have a similar advertising avalanche in India promising “The Elixir Of Life” that seems to have targeted family physicians and obstetricians. How about the Indian College of Obstetricians & Gynecologists or the Media taking a stand with an Indian Opinion Paper?

Saturday, June 30, 2007

From The Ganges To The Thames

Today my blogging attempt will be to touch your heart with facts that should make you proud of your race & the
country. Let me begin by asking you a few questions:

Who is the General Manager of Hewlett Packard (HP) ?
A. Rajiv Gupta

Q. Who is the creator of the Pentium chip (needs no introduction as 90% of the today's computers run on it)?
A. Vinod Dham

Q. Who is the third richest man on the world?
A. According to the latest report in Fortune Magazine, it is Azim Premji, who is the CEO of Wipro Industries. (the Sultan of Brunei is at the 6th position now!)

Q. Who is the founder and creator of Hotmail (Hotmail is the world's No.1 web based email program)?
A. Sabeer Bhatia

Q. Who is the president of AT & T-Bell Labs (AT & T-Bell Labs is the creator of program languages such as C, C++, Unix to name a few)?
A. Arun Netravalli

Q. Who is the new MTD (Microsoft Testing Director) of Windows Vista, responsible to iron out all initial problems?
A. Sanjay Tejawrika

Q. Who are the Chief Executives of CitiBank, Mckinsey & Stanchart?
A. Victor Menezes, Rajat Gupta, and Rana Talwar.

We Indians are the wealthiest among all ethnic groups in America, even faring better than the whites and the natives:

There are only 3.22 million Indians in the USA (15% of population) .. Yet,

38% of doctors in USA are Indians, 12% scientists in USA are Indians, 36% of NASA scientists are Indians, 34% of Microsoft employees are Indians, 28% of IBM employees are Indians, 17% of INTEL scientists are Indians, 13% of XEROX employees are Indians.

Some of the following facts may be known to you. These facts were recently published in a German magazine, which deals with world history facts about India:

1. India never invaded any country in her last 1000 years of history.
2. India invented the Number system. Zero was invented by Aryabhatta.
3. The world's first University was established in Takshila in 700BC. More than 10,500 students from all over the world studied more than 60 subjects there. The University of Nalanda built in the 4th century BC was one of the greatest achievements of ancient India in the field of education. Our present President wants to take up a teaching post in this University after he finishes his post.
4. According to the Forbes magazine, Sanskrit is the most suitable language for computer software.
5. Ayurveda is the earliest school of medicine known to humans.
6. Although Western media portrays modern images of India as poverty striken and underdeveloped through political corruption, India was once the richest empire on earth.
7. The art of navigation was born in the river Sindh 5000 years ago.. The very word "Navigation" is derived from the Sanskrit word Navgatih.
8. The value of Pi was first calculated by Budhayana, and he explained the concept of what is now known as the Pythagorean
Theorem. British scholars have accepted officially in 1999 and published that Budhayan's works dates to the 6th Century which is long before the European mathematicians.
9. Algebra, Trigonometry and Calculus came from India . Quadratic equations were by Sridharacharya in the 11th Century; the largest numbers the Greeks and the Romans used were 106 whereas Indians used numbers as big as 1053
10.According to the Gemological Institute of America, up until 1896, India was the only source of diamonds to the world.
11. USA based IEEE has proved what has been a century-old suspicion amongst academics that the pioneer of wireless communication was Professor Jagdeesh Bose and not Marconi.
12. The earliest reservoir and dam for irrigation was built in Saurashtra.
13. Chess was invented in India
14. Sushruta is the father of surgery. 2600 years ago he and health scientists of his time conducted surgeries like cesareans, cataract, fractures and urinary stones. Usage of anaesthesia was well known in ancient India .
15. When many cultures in the world were only nomadic forest dwellers over 5000 years ago, Indians established Harappan culture in Sindhu Valley ( Indus Valley India in 100 BC).


In the recent history, very rarely India has come across a situation, all at a time, an ascending economic trajectory, continuously rising foreign exchange reserve, reduced rate of inflation, global recognition of the technological competence, energy of 540 million youth, umbilical connectivities of 20 million people of Indian origin in various parts of the planet, and the interest shown by many developed countries to invest in our engineers and scientists including setting up of new R&D centers. Above all India as the largest democracy in the world, has a reputation for its democracy and for providing leadership for the one billion people with multi- cultural, multi-language and multi-religious backgrounds. Our
technological competence and value systems with civilizational heritage are highly respected. Foreign Institutional Investors find investing in India attractive. Indians are also investing in companies abroad and are opening new business ventures. Tata's Corus & Kumaramangalam Birlas take-overs are just a preview of what is going to follow. As per the report titled "From the Ganges to the Thames" which states that the Indian Foreign Direct Investment in British capital is second only to that of the US and Indian FDI project in Europe has increased from just 5 to 119 during the period 1997 to 2004. The Government is also committed to economic development by ensuring growth rate of 7% to 8% annually, enhancing the welfare of the farmers and workers and unleashing the creativity of the entrepreneurs, business persons, scientists, engineers and
other productive forces of the society. We must use this opportunity for transforming India to a globally competitive developed nation before 2020. This calls for the agriculture, manufacturing and service sectors becoming globally competitive leading to an economically competitive environment. What then would be the profile of the globally competitive developed India?

1. A Nation where the rural and urban divide has reduced to a thin line.
2. A Nation where there is an equitable distribution and access to energy and quality water.
3. A Nation where agriculture, industry and service sector work together in symphony, absorbing technology thereby resulting in sustained wealth generation leading to greater high value employment opportunities.
4. A Nation where education is not denied to any meritorious candidates because of societal or economic discrimination.
5. A Nation which is the best destination for the most talented scholars, scientists, and investors from all over the world.
6. A Nation where the best of health care is available to all the billion population and the communicable diseases like AIDS/TB, water and vector borne diseases and other stress diseases, cardiac diseases, cancer and diabetes are brought down.
7. A Nation where the governance uses the best of the technologies to be responsive, transparent, fully connected in a high bandwidth e-governance grid, easily accessible and simple in rules, thereby corruption free.
8. A Nation where poverty has been totally eradicated, illiteracy removed and crimes against women are absent and the society feels unalienated.
9. A Nation that is prosperous, healthy, secure, peaceful and happy and continues with a sustainable growth path.
10. A Nation that is one of the best places to live in, on the earth and brings smiles on a billion plus faces.

It is indeed a big challenge of high magnitude. For achieving such a competitive profile for India, we have a vision of realizing this goal in a time bound manner. Only a heathy nation will transform into a developed nation. Unless the maternal & child health statistics compare with the developed world, we will never achieve that status. Here is where we obstetricians and gynecologists come in. We are indeed the pillars upon which the the health of the nation rests on. Let us work with the government in transforming our BIMARU states across timelines and bring them at par with healthcare in the metros. This is achievable. The administration is committed and irrespective of the party in power, the reforms will go on. The type
of mission in front of us is very complex and challenging. Let us share a great thought propounded by Saint Maharishi Patanjali in the Yoga Sutra in 500 BC:
"When you are inspired by some great purpose, some extraordinary
project, all your thoughts break their bounds. Your mind transcends
limitations, your consciousness expands in every direction, and you
find yourself in a new, great and wonderful world. Dormant forces,
faculties and talents come alive, and you discover yourself to be a
greater person by far than you ever dreamt yourself to be."

But we need to do a RDB (Rang De Basanti) to go ahead - Today I wish Sanjay Gandhi was alive.

Friday, June 29, 2007

Testicles Forever?

A recent report on possible therapeutic uses of testicular stem cells helps to highlight the level of confusion and lack of focus
in stem cell biology today. Sources of stem cells such as embryos, testicles and ovaries are technically difficult to manipulate and have worrying, potentially malignant properties should they ever be transplanted to a human being. These stem cells also carry significant moral, ethical, legal and religious objections to their creation and use. UK researchers have been given the go-ahead to investigate the potential of human testicle stem cells to develop into other types of body tissue. The Human Fertilization and Embryology Authority (HFEA) has licensed the team, based at the Hammersmith Hospital in London, to
study the cells in order to find out if they are as versatile as stem cells isolated from early embryos. The scientists hope that the work may eventually lead to new therapies for conditions such as heart disease, Parkinson's disease and spinal injury.
Last year, German researchers isolated cells from adult mouse testicles that share some of the characteristics of embryonic stem (ES) cells. The team isolated stem cells that normally grow into sperm, and coaxed them into producing many different types of body cell. The researchers, based at the Georg-August-University of Goettingen, published their findings in the journal Nature. However, at the time, other scientists cautioned that stem cells from human testes might not behave in the same way as their mouse counterparts. The Gottingen team used genetically altered mice in which the sperm stem cells were permanently 'tagged' with a fluorescent protein, to enable them to isolate the elusive cells from mouse testes. They then grew the cells in the laboratory, and found that some of them resembled ES cells. These cells, which they dubbed multipotent adult germline stem cells (maGSCs), were able to grow into several different types of body cell - including heart, brain, liver and skin. The scientists also found that the maGSCs were able to form different tissues and organs when injected into mouse embryos. The ongoing controversy surrounding research into human ES cells in Germany, where such work is banned, and many other countries, has lead several groups to seek alternative sources of cells that can potentially develop into a wide range of different tissues. Even in countries where ES cell research is permitted, it hinges on the availability of donated human eggs.

There is another source of stem cells which is hardly ever mentioned in the news and is currently being discarded on a daily
basis. It has no moral, ethical, legal or religious objections to use and it has been transplanted safely over 6,000 times to date to treat 45 different diseases. This source of stem cells is human umbilical cord blood. Cord blood can be collected at every birth with no risk or pain to the mother or baby. Once collected cord blood is processed using tried and tested technology and can be frozen in liquid nitrogen for many years. Current applications of these stem cells are in the treatment
of leukemia, related blood disorders and the repair of the bone marrow following high dose chemotherapy for cancer. Perhaps the most important aspect of cord blood is that it contains mesenchymal stem cells capable of producing many cell types including neuronal and muscle tissue. These cells have an availability and potential far greater than embryonic or testicular stem cells and we must focus our time, energy, resources and expertise on the full utilization of these priceless stem cells. Cord blood stem cells are currently being assessed in a clinical trial in Canada in the treatment of multiple sclerosis. The umbilical cord itself also contains stem cells capable of producing a range of tissue types, most
notably bone tissue. If stem cell biology is to advance we must begin to collect, store and carry out research on as much cord blood as possible. According to advocates of umbilical cord blood banking, we have a readily available source of stem cells with massive potential which is currently, for whatever reason, being ignored by researchers, media and politicians alike. “We must stop talking about esoteric sources of stem cells and focus on cord blood stem cells as the source of stem cells for current therapeutic applications and ground breaking therapies of the future.”

Commenting on the planned research at Hammersmith Hospital, stem cell expert Professor Harry Moore, of Sheffield University, said: 'In this country, the ethical issues of obtaining stem cells from cloned embryos are really covered by the
HFEA, but there is still the major problem of where do you get eggs that are high enough quality and in sufficient quantity. The advantage of this work on human testicular cells is that it avoids both of these issues'. If testicular stem cells prove to be as versatile as their embryonic counterparts, it may be possible for men to bank testicular tissue early in life, and later use it to repair damaged or diseased areas of the body. Such tissue could also potentially be used to provide cell-based therapies for any men who share the same tissue type. Professor Chris Barratt, of the Birmingham Women's Hospital told the Guardian newspaper: “There are a lot of testicles around and you don't need a staggering number to have enough variety to match nearly all of the population”. In India, we have much larger numbers.

Thursday, June 28, 2007

Asymmetrical People make Jealous Lovers & Handsome Men have the best Sperm!

Asymmetry could account for a fifth of the variation in romantic jealousy from person to person, says a Canadian researcher. Just about everyone is lopsided to some extent. But in recent years, a series of animal and human studies have suggested that the implications of asymmetry go far beyond struggling to find shoes that fit both feet. It seems that people who are more symmetrical are not only healthier, more fertile and perhaps even smarter - they are also more attractive. This led William Brown at Dalhousie University in Halifax, Nova Scotia, to wonder about jealousy. "If jealousy is a strategy to retain your mate, then the individual more likely to be philandered on is more likely to be jealous," he speculated. And if people who are less symmetrical are less desirable, they are more likely to be cheated on. To test his theory, Brown looked at 50 men and women in various kinds of heterosexual relationships, comparing the sizes of paired features such as feet, ears and fingers. The volunteers then filled in a questionnaire already used in other studies to assess romantic jealousy. He found a strong link between asymmetry and romantic jealousy. Asymmetry could account for over a fifth of the variation in romantic jealousy from person to person, he says. To make sure less symmetrical people are not simply cursed with more jealous personalities, Brown also assessed their propensity to be jealous outside the relationship, in the workplace for example. But the less symmetrical people were no more likely to be jealous in general, he found, than more symmetrical folk.
A separate study by UK researchers has revealed that women with the most alluring voices have the most attractive faces. Sarah Collins and Caroline Missing, at the University of Nottingham, played recordings of 30 young women to men who later saw their photos. The men judged women with attractive voices as the best looking, reveals the study published in the latest Animal Behaviour.
Beauty really is in the eye of the beholder. Rather than always chasing the best-looking members of the opposite sex, some animals prefer mates that the majority find decidedly unattractive. Studies of how birds, fish and people choose mates have found that members of the same species tend to find the same things attractive. For instance, peahens prefer to mate with brightly colored, long-tailed peacocks, while women prefer tall men. Those attractive traits are supposed to signal beneficial characteristics such as an increased chance that any offspring will survive. Male lions with long, dark manes are more attractive to females and more intimidating to rivals, US research involving dummy animals shows. Manes vary from light blond to black and can be up to foot long. The research team planted pairs of life-sized toy lions with different types of mane near males and females in the Serengeti National Park in Tanzania, and monitored the lions reactions to the 'intruders'. In all cases, males preferred to approach dummies with lighter, less shaggy manes. But females did the opposite. They preferred to approach darker males, suggesting they are a better bet as a mate. Next, the team examined data on blood samples from several dozen males that had been sedated. They found a strong correlation between blood testosterone levels and mane color.
According to a recent news story in the New Scientist, 'handsome men have the best sperm'. And how do we know this? Because researchers recruited 66 women in Valencia, Spain, who looked at the faces of 66 male students and happened to identify as the most handsome those men who also have the best sperm. The authors of the study conclude: 'Our study has shown that women are able to recognize reproductively fit males on the basis of their facial appearance alone.'
It's difficult to see how they could come to such a conclusion. In the study, 66 women made a subjective assessment of the attractiveness of 66 men; and the men they judged to be most good looking happened to have more motile and more morphologically normal sperm. All the research shows, therefore, is that in a small sample of young men, good looks seems to correlate with good sperm. What we don't know from the New Scientist story is other information that might be relevant, such as how much the men smoke or drink. Intriguingly, the study doesn't show a correlation between good looks and a good sperm count - a measurement often used as an indicator of male fertility.
Studies such as these are becoming increasingly common in the media today. But why we are so interested in them? Perhaps drawing grand conclusions from such research findings fulfils a need in us to find causes for our behavior that are not the result of our own free will and for which, consequently, we don't have to take responsibility. In this case, our search for causes of human behavior that are beyond our control leads us to conclude that women are attracted to handsome men for sound biological reasons. It can't possibly be that we are simply driven by such shallow reasons as the desire to be surrounded by beautiful things, can it?

Wednesday, June 27, 2007

The Great Verna Promotion from Hyundai Motors

I recently became a sucker to full page advertisement promotions by Hyundai Motors India Limited. Let me tell you this interesting story. In fact it will be more readable as I take you along-with two letters that I wrote to the "customer relations" of Hundai motors & am yet to receive any feedback. Letter 1 - "I am a gynecologist practicing in the city of Mumbai. I have
previously owned cars from the Maruti Co., Honda as well as the Mercedes Benz. On May 16, I booked the Verna CRDi Sx model from Jayabharat Automobiles. I was told that the waiting period is two weeks but if I make a complete down-payment for the car, I would probably get the car within 10 days. I gave them the full payment by check on May 16, 2007. The car was booked in my personal name. No one contacted me till I went to the dealership myself after 6/7 phone- calls in the first week of June 2007. Everytime I would make a call, someone would promise me they would call back and never did call. The car was finally delivered on June 13, 2007. The dealership is a shame on your company. The attitude of the staff is like a Government of India office ten years ago. No one is driven or is customer attentive- the whole atmosphere is Babu-like!
My car has two major problems. The auto function of the Climate-Controlled A/C is not working and the polyglass covering the Milometer-Odometer panel is defective (opaque in parts like some chemical has corroded parts of it. I wonder how did it get past the quality checks. Never before for any of my previous 8-9 cars did I ever have a problem in a brand new purchase.
I do not want to get any services or trouble-shooting done with Jayabharat. Please recommend another dealer/workshop where I can send my vehicle for the rectification of problems.
I hope your customer care is not like the dealership:(
I look forward to hearing from you.
Sincerely yours,
GNA"
I got a reply that someone from Jayabharat would contact me. The story continues thus-I wrote again to the "customer relations" cell - Letter2 -
"I got a call from the Jayabharat workshop and had visited the same. Mr Ashokan there was extremely courteous and receptive to the complaints. He mentioned that the polyglass is not available separately and the entire milometer/odometer assembly needs to be ordered from Chennai and he would write to the factory. I have not heard from them again.
The "automatic" climate control problem could not be solved! He made me speak to a Hyundai Motors representative who explained that the A/C was not defective but was set to European standards & nothing canbe done about it. Let me explain again what the problem is to me &possibly to all end-users. Till 21 degrees Celcius, the A/C works as an automatic climate controlled A/C and automatically adjusts the blower speed to reach the preset temperature between 17-21 degrees Celcius. The moment we set the temperature to 22 degrees or more, the Automatic Function is disabled automatically & the A/C moves automatically to the Fresh-air mode and starts pulling in air from the outside! Imagine driving in Mumbai with the temperature set to 22 degrees and getting Diesel & Petrol fumes being sucked in. This is very unfair to the customer. I was explained by the Hyundai representative, that after 21 degrees, I could very well move to a manual function!
Sir, the only reason I paid some extra money for the CRDi Sx model was the climate controlled A/C. If I wanted to use the regular car A/C, I would have bought your regular diesel Verna. I drive other vehicles like the Honda CRV, Honda Accord, Mercedes Benz C 220 CDi -all with automatic climate controlled A/Cs, but none of these A/Cs switch to a manual mode after 21 degrees Celcius! Please give me a satisfactory explanation. I'm sure your engineers can set the problem right. There is no other vehicle on the Indian roads with a malfunctioning automatic climate controlled A/C such as in the Verna CRDi Sx model if the above explanation is true. I look forward to your response."
I have since written twice more to their "customer-relations" cell, but there is no response. The company believes in no customer-relations. Their existence is only till the great Indian customer reads their color ads in National dailies & color hoardings in the city and buys one of their cars. Post sale, there are only suckers like me writing letters to the motor company, blogs & letters-to-the editors of National dailies, hoping someone exposes the mighty Koreans.

Tuesday, June 26, 2007

Stem cells: Miracle postponed?

In the light of the Korean stem-cell scandal, many big claims about stem cells are looking decidedly doubtful. Hyeoni Kim believed that the miracle cure for his paraplegia was around the corner. He had been paralyzed at just 8 years old when he was hit by a car on his way home from school. So when South Korea's science superstar, Woo Suk Hwang, asked if his team could take skin cells from Kim and use them to obtain stem cells that might one day provide a cure, Kim and his family were delighted. When Hwang visited him in hospital in April 2003, the boy, then 9, asked him if he would walk again. "I promise," Hwang replied. That promise became immortalized in a Korean postage stamp showing a man rising from his wheelchair. But it was always highly questionable. Even if Hwang had managed to derive cloned embryonic stem cells (ESCs) from the skin cells of Kim and 10 others - as he claimed in May 2005 - he would still have been a long way from mending Kim's paraplegia.
Stem cell science has been hailed as modern medicine's best hope - to treat the untreatable, to keep us fit in old age and even, perhaps, to help the severely disabled to walk again. But scandal in South Korea has rocked this science - with one of its leading proponents labeled a fraud, and as the scientists reflect on the ethics of their work and its practical limits, where does this leave all of us, the potential patients?
Stem cells, unlike ordinary cells, have the unique power to re-create themselves when they divide. There are two types: the first, adult stem cells, are cued up to become particular cell types - say nerve, blood, bone or heart. These can carry out valuable repairs - but only in their specialist part of the body. The second group is embryonic stem cells. Found in the early human embryo, these are highly sought after because they can re-create themselves indefinitely. Also, since they are not yet switched to become specific cell types, they have the potential to repair damaged and diseased organs anywhere in the body.
Dr Hwang claimed to have created 11 stem cell lines from human embryos, cloned so that the cells exactly matched an individual patient - the Holy Grail of stem cell science. It turned out much of his work was fake, and crucially that he'd had to use far more human eggs than he'd said. The challenge now, for embryonic stem cell scientists at least, is to find ways to make stem cells without using vast quantities of human eggs - in short supply and, for some, ethically questionable. Until now, scientists have relied on creating stem cells from left over embryos from IVF. Before the Hwang expose, researchers had hoped to join the elite club of scientists using cloning to study the cellular processes behind disease. Now, to avoid using up human eggs on an uncertain technique, most workers have a plan for a new - and potentially controversial - way around that: cloned human-animal hybrids. Researchers now would like to use non-human eggs - for instance rabbit eggs. But therapies are at least 10 years away. A team at the University of Cambridge has another plan. Roger Pedersen, director of the centre for stem cell research at the university, told us about a plan that avoids cloning, and fresh human eggs, and relies instead on off-the-shelf matches from a bank of stem cell lines from selected donors. Then there's the man with a third way to avoid the need for human eggs. Mohammed Taranissi runs one of the UK's most successful fertility clinics. He's promoting what he calls "stem-brid" technology, which uses the stem cell line itself as a surrogate egg. But there's a new realism now among embryonic stem cell scientists about how long it will be before they can help people.
That leaves their counterparts working on adult stem cells. They now expect to deliver treatments much sooner. One team, at the London Chest Hospital, is using adult stem cells taken from a patient's own bone marrow to try to repair the damage caused by a heart attack. Dr Anthony Mathur is the cardiologist in charge of the trial - the largest of its kind in the world. He is quoted as saying: "My passionate feeling here is that this type of therapy, cellular therapy, is going to revolutionize the way we practice medicine." Half the patients are treated with stem cells and half with just the fluid, or growth factor in which the cells are found. Neither Dr Mathur nor the patients know who's getting what but that's crucial in order to gather definitive, scientifically controlled data. Across London, another adult stem cell trial could yield results within months. At the Institute of Neurology, they hope to use unique adult stem cells from the lining of a patient's own nose to treat nerve and spinal cord injury. Professor Geoffrey Raisman, who's leading this research was quoted on BBC: "The interest in embryonic stem cells has led to adult stem cells being very much neglected. And whereas I think for embryonic stem cells we're talking about a long time ahead before these cells are going to be in use, in our case we're thinking of clinical trials within this year." It would seem a safe bet that adult stem cells will deliver first - but the enthusiasm for this science as a whole is still there, despite the reality check brought about by Dr Hwang.
I agree completely with Prof. Roger Pedersen from Cambridge who says: “We hope that discoveries that are made quietly and without the glare of lights... will ultimately change the way we treat diseases”.

Monday, June 25, 2007

Cytoplasmic Transfer

It was recently reported in the journal "Human Reproduction" that cytoplasmic transfer could be used to transfer healthy mitochondria (small structures that power the cell) into certain infertile women's eggs. This has resulted in 30 healthy children that were "born from three parents". This pioneering work into fertility treatment was conducted at Institute for Reproductive Medicine and Science of St Barnabas, in New Jersey. The 30 children born were actually the first human babies ever whose genetic makeup has been artificially altered. Even though the babies were born healthy (and without this novel technique would not have existed at all), the cytoplasmic transfer technique was condemned as unethical by some opponents, who said it amounted to human cloning (BBC). However, cytoplasmic transfer and nuclear transfer are NOT the same thing, and the genetic makeup of mitochondria does not govern key aspects of the child's development, like intelligence, personality or physical form. These things are predominately determined by nuclear genes, and these genes were not altered in the children. Cytoplasmic transfer is certainly not cloning, as has been suggested, but it is a useful fertility technology for certain women affected with mitochondrial diseases. Cytoplasmic transfer is a logical extension of assisted reproduction, a procedure that represents a hybrid between in vitro fertilization in its traditional form and IVF using donated oocytes. As the IVF procedure has improved, several groups of patients continue to pose huge challenges. One such group is characterized by normal FSH levels and normal responses to stimulation. Patients have lots of follicles when stimulated and high estradiol levels, but poor subsequent embryo development. For years these women, after numerous failed cycles, had no alternative but to discontinue treatment. Oocyte donation, now a common procedure, offered these women a viable procedure, one with a high pregnancy rate. Unfortunately, oocyte donation includes the disadvantage of losing the mother's genetic link to the child, as the genes of the donor are passed on to the child born through the procedure.
Two potential reasons account for poor embryo development. Studies of the genetic component of many of the eggs in women with persistent poor embryo development showed that eggs with abnormal chromosomes often made poor embryos. However, this was not always true. Many eggs with normal chromosomes also developed poorly. Logically, the reason may lie in the cytoplasm, the area within the shell of the egg that lies outside of the nucleus, outside of the region that contains the genetic material or DNA. The cytoplasm includes several components. One component is mitochondria which provide energy to the cell, fuel for many of its functions including, presumably, cell division. In theory, a deficiency in mitochondria may leave a cell without the necessary fuel to power its own division after fertilization, resulting in abnormal division. This abnormal division then results in an accumulation of fragments from the dividing cells and a poor chance of further development after embryo transfer.
Another important component of the cytoplasm is the spindle apparatus, a sort of railroad track within the cell, along which the chromosomes separate. The steps in cell division include the duplication of the chromosomes and the subsequent distribution of the genes equally between the two daughter cells. If an egg contained normal chromosomes but had inadequate mitochondria to power cell division or a defective railroad track system for the chromosomes to divide, would this not result in poor embryo formation? And if the cause of the egg problem was in the cytoplasm, then why not replace just the cytoplasm instead of the whole egg, thus keeping the mother's own genetic contribution to the pregnancy? This is the premise behind the development of cytoplasm transfer by Jacques Cohen & his group from St. Barnabas, New Jersey, USA. But the journey from good idea to actual pregnancies has been long and complex. As in many of the procedures in assisted reproduction, much of the initial research came from our colleagues in veterinary medicine. Two methods of cytoplasm transfer were developed, one which transfers a small amount of cytoplasm by tiny needle from the donor to the recipient egg, the other transfers a larger amount of cytoplasm which is then fused to the recipient cytoplasm with electrical impulses.
As a step forward in the refinement of assisted reproduction it is a huge step, and presently, only a relatively small group of people will benefit from it. As the process of cytoplasmic transfer is further refined it will help many others. Important questions need to be clarified. What we most want to know is how will this technique work with the poorer responders? Can cytoplasm transfer affect the poor results we consistently see in patients with elevated FSH levels? And what exactly is in the cytoplasm that might make the eggs "better?" Can we someday hope to find a source of that substance that does not
require the expensive and cumbersome process of using a donor's eggs? For now, we can only give the unsatisfying answer that we'll have these answers sometime in the future. For those of us struggling with the frustrations of infertility now , we can only hope that the future is sooner rather than later.