India Stem Cell Lab at Forefront
By LAURINDA KEYS
Associated Press Writer

September 7 2001, 12:20 PM PDT

BOMBAY, India -- Up the unguarded staircase of a gray concrete building, past peeling yellow paint and corners stained with betel nut juice, India hides a treasure that may be worth millions of lives -- and dollars.

Seven prospective human embryonic cell lines are developing in a steel-encased glass box in the Reliance LifeSciences laboratory behind locked, unmarked doors.

The laboratory is one of 10 identified by the U.S. National Institutes of Health as having possible human embryonic stem cell lines that American researchers can use for research under federal grants.

In India, a developing nation of 1 billion people, it's common to find designer business offices and antique-filled apartments hidden in buildings with crumbling plaster.

It's also common to find internationally trained scientists and doctors doing vanguard work.

Among them is Dr. Firuza Parikh, founder and director of Reliance LifeSciences Pvt. Ltd., funded by Reliance group, a major Indian corporation.

The development of stem cell lines began in April, with 10 scientists, headed by Dr. Satish Toety, who worked with mouse embryos for a decade. Forty more scientists are working on other projects.

Parikh credits the rapid development of the lab's prospective stem cell lines to committed scientists and good funding. Four lines are robust, dividing and developing into colonies, she said; the other three are "immature."

Reliance group has invested $5 million in the laboratory and plans to spend $25 million more in the next few years, said senior executive vice president K.V. Subramaniam.

"We're not looking at an immediate return," he said. Clinical trials to seek better treatments for inherited blood disease, diabetes or burned flesh are three to five years away.

It will take six to eight months for the laboratory to know whether it has developed self-perpetuating stem cells that can grow into cells for any part of the human body.

Parikh said four cell lines are doubling every 36 hours, are free of disease and have gone through six to eight "passages," meaning they have multiplied without diversifying into specific cell types and have been separated into new colonies.

"The success rate is good, about the same as reported by the Israeli and Australian groups," said Dr. Robin Lovell-Badge, a stem cell researcher at Britain's National Institute for Medical Research. "But having a couple of colonies growing is not the same as having a cell line characterized as being useful."

Parikh agrees. "Before sharing our cell lines with other investigators, we want to ensure that these cell lines are characterized properly," she said.

That means verifying they will keep multiplying indefinitely, have a normal number of chromosomes and differentiate into specific cell types when needed.

The Reliance laboratory envisions developing therapies or cures for thalassemia, an inherited blood disease prevalent in Asia, and diabetes. Development of skin cells for treatment of burns and wounds is another research possibility.

"There is nothing on the cards yet, but we are talking to several U.S. institutions and companies for collaborative research," said Subramaniam.

Parikh said her lab held a video conference with the U.S. National Institutes of Health a week before President Bush identified 10 laboratories with 64 possible stem cell lines that met funding requirements.

Embryo donors had to be fully informed about the nature of the research and receive no compensation. The stem cells had to be extracted -- a process that kills the embryo -- before Aug. 9.

Parikh was hiking near Bombay with her physician husband and three children when Bush made his announcement. When she returned, she didn't realize why journalists from around the world were calling her.

"It's getting a little bit out of proportion, as if it was a secret for so long," she said. "This entire work, even in the U.S., only started in 1998."

It may be too early to get excited, Lovell-Badge said.

"We just don't know enough about the details of most of the cell lines, how they have been made, how they were grown, where they come from, what they can do," he said. Work on only about a dozen lines has been published.

The other lab in India identified by the Bush administration for U.S. government-funded research is the National Center for Biological Sciences in Bangalore. It has said only that it "may have three potential human stem cell lines" derived from frozen embryos.

"No one can say whether the lines in India, or elsewhere, are going to be good or bad until we've tried to do something with them and preferably other scientists have had a look at them," said Lovell-Badge.

He said the number of "passages" that four of Reliance's lines have achieved is encouraging, and the lab's anti-contamination protocols and extensive consent forms are important quality checks.

The lab, which opened in January, occupies 20,000 square feet of Sir Hurkisondas Nurrotumdas Hospital and Research Center.

Visitors can wander up the unguarded stairwell to the third floor, where a sign over an open doorway says, "Reliance Project Office," and new swivel office chairs, some still covered in plastic, line the hallway.

Visitors are not allowed in the laboratory and offices on the fourth floor where embryonic cells are obtained from patients in private.

Dressed in sterile white, scientists nurture prospective stem cells -- like pinpricks in petri dishes of pink mouse-based nutrient _ as they divide and multiply into colonies.

When a colony grows to 10,000 cells, they are "passaged," or separated and transferred to new dishes.

The colonies can be passaged up to eight times before they are characterized by certain markers as an embryonic stem cell line. The lab's cell lines are in their fifth to seventh passages, Parikh said, meaning some are close to being characterized.

"It's like a bar code on a chocolate bar," she said. "The code or marker tells you this is a Cadbury's or something else. Stem cells will have certain markers."

In a 2{-minute videotape, scientists are seen using robotic instruments under an inverted microscope.

Pipettes thinner than human hair suck up the cell colonies and transfer them to new containers. Then they are stacked in a glass, steel-covered box that keeps them at 99 degrees Fahrenheit.

The process begins with Parikh's patients in the assisted reproductive center.

"We tell them the research may not lead to anything, but maybe they will be making an important contribution to something later on," she said. "We have a very exhaustive informed consent form, six or seven pages."

All the donors are Indian. She would not reveal their number, but said 21 embryos were used to develop the seven stem cell lines.

Doctors treating infertile couples produce more than enough embryos, then choose to implant those with the best chance to develop in the uterus.

Leftover embryos can be used for research if the stem cells in the inner nerve mass are extracted and used immediately, or frozen in liquid nitrogen at five days old.

Parikh looks forward to collaboration and discoveries of cures for chronic diseases.

"I hope it happens in my lifetime," she said. "The first 25 years of this century would really belong to stem cells."

Copyright 2001 Associated Press

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Stem cells: To be or not to be

India could be the biotech factory of the future

Manjari Raman
Manjari Raman

Picture 2025 AD: The memory of the pot-holed, gutted National Highway 1 has all but faded. Instead, a ten-lane expressway, called the Golden Artery cuts an asphalt swathe from Kashmir to Kanyakumari. The arid, fallow fields by its banks are gone too, replaced by bio-tech farms housed in low, grey, windowless buildings. Every day, each farm harvests a lucrative crop of stem cells which are then grown into hair, teeth, bone, blood, muscle and marrow. These cell factories have powered India’s breakneck entry into the top ten richest nations of the world. What Taiwan once was to motherboards and China to Barbie dolls, India now is to stem cells: the worlds largest production base for human spare parts.

The funny thing is you really don’t need too much imagination to conjure up this scenario. For even as the leading nations of the world mull over how humane it is to pursue human cloning, India has an opportunity to wrest the global competitive advantage by turning its laboratories into bio-tech factories. Let the US worry about interfering with Nature; for India, the choice is clear. Its better to worry about the suffering millions than to care about the unborn cell.
The embryo, so to say, for this body of thought, springs from two events last week. After a protracted, often anguished debate, the US House of Representatives finally voted to ban human cloning in the US — totally. But while that might have been a vote in favour of preserving human sanctity assuming the human soul is worthy of preservation, it also raised a question mark on the future of embryonic stem cell research in the US.

Essentially, embryonic stem cell research involves using human or animal embryos to grow various kinds of cells in a tumor and then harvest them to repair human tissue. It is not just about spare parts of course. Such research lies at the core of finding cures for cancers and other ailments like Parkinson’s, Alzheimer’s and heart disease. But while the House clearly clamped down on human cloning — the new legislation imposes a fine of atleast $1 million and a prison sentence to up to 10 years on anyone who tries to clone a human Dolly (Parton) — Capitol Hill still faces an even more sticky issue: to ban or not to ban cloning of human cells for therapeutic research purposes.

The second significant event took place halfway across the world. On August 1, a Japanese Cabinet panel on bio-ethics approved guidelines to allow stem cell research. The Japanese model of safe-guards: embryonic cells used in research would be taken only from those made for fertility treatment and that would be otherwise discarded; research on cloning humans, or creating sperm and eggs would be strictly banned; and selling stem cells would be banned. If all goes as per schedule and when it comes to technology, (in Japan it often does), Japanese scientists could start on stem cell research as early as the end of 2001. In other words, the race for the next big idea for nations is on and India must now decide whether it wants to jump in and take a lead or watch from the sidelines.

The DNA of competition favours us, by the way. One, bio-tech is nothing but software now, and we have a solid building block in that. Two, Indian pharma companies have won recognition already for their ability to innovate and offer quality research with a cost-advantage. Three, should countries like the US decide to ban stem cell research, the action will not stop, only migrate. Companies like Boston-based Advanced Cell Technologies which is already deeply committed to cloning experiments on human embryos have already worked out an alternate strategy should the ban on stem cells come into effect. Plan B doesn’t involve shutting down the lab: instead, they plan to move it lock, stock and test-tube block, to Britain, where the research climate is friendlier.

India could be one such safe harbour too, starting first with offering an environment for research and later when the technology evolves sufficiently, by becoming a high-quality site for mass producing stem cells. Of course, the country would first have to debate the rights or wrongs of the issue: what part of embryonic research is humane and acceptable to the Indian psyche? Given our pro-abortion mindset, will we even have to worry about touchy-feely issues of whether the human embryo has a soul? Which part of the stem-cell value-chain would work best for us? What would we gain in terms of national income, jobs, quality of life, national pride and economic development by pursuing a well thought-out, strategy in bio-tech?
Remember: with nearly 40 per cent of the world population expected to be over 60 years old by 2070, there is a growing market out there for human spare parts. India can afford to be neither squeamish nor sluggish if it wants to tap the root of the budding opportunity.