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The Wild West of stem cell procedures

From street-side stem cell clinics promising people in wheelchairs that they will walk, to corporate cord blood banks that offer to store your baby’s umbilical cord blood, an unethical and unregulated industry in stem cell procedures is feeding off the desperation of Indian patients. A comprehensive regulatory structure is urgently needed, writes Sandhya Srinivasan

On August 17, 2010, a Bangalore hospital announced what it suggested was a major medical breakthrough: it had used stem cells to successfully treat four children with thalassemia, a blood cell disorder for which the children would otherwise have painful blood transfusions for the rest of their lives. The hospital’s director was quoted in the press as saying that newer indications for stem cell therapy are breast cancer, renal cell cancer, heart disease, spinal injury, Parkinson’s disease and Alzheimer’s disease. According to the hospital’s website: “As stem cell transplants become more routine, they may be used to fight lung cancer, sickle cell anaemia, multiple sclerosis, lupus, AIDS and many genetic diseases.”

These are incorrect and misleading statements that will give false hope to people with such conditions.  

It is true that stem cell technology has proved effective in certain conditions. The special qualities of these immature cells, found in various parts of the body including the bone marrow, umbilical cord, foetus and embryo, are being researched for the treatment of a number of diseases. Stem cell therapy can be autologous, from the person’s own body, or allogenic, donated by a person whose tissue type is matched as closely as possible to the recipient to prevent rejection of the transfusion. 

But little of what gets publicised today comes from systematic research with proven safety, effectiveness and realistic levels of success. Much of what we are seeing is the unethical promotion of stem cells as miracle cures.  

On the one hand, street-side stem cell clinics promise the wheelchair-confined that they will walk. On the other hand, corporate cord blood banks exploit the market for ‘bio-insurance’: store your baby’s umbilical cord blood -- for a fee -- just in case s/he falls ill with some terrible disease that might be cured through the use of those cells. The picture is one of unethical and unscientific medical practice, false advertising, misrepresentation, and the exploitation of people’s desperation, hopes and fears. The publicity generated by such hype helps business. 

At the same time, the practice of established therapies, such as bone marrow transplantation, can have ethical implications that need urgent discussion.  

Bone marrow donation by children 

Going back to the Bangalore hospital, the children were cured after they received transfusions of stem cells extracted from bone marrow -- one received the transfusion from his grandmother and the others from their siblings aged between 12 and 14 years.  

The hospital managed to get the story covered widely; the haematologist is quoted as saying that their experiences with the four children “now prove the therapeutic potential of bone marrow-derived stem cells, from a matched donor”.  

Bone marrow transplant for certain blood conditions is one of the few established indications for using stem cells. So there’s nothing medically new to report about doing bone marrow transfusions for children with thalassemia.  

But there are other issues to comment on in this account. For one, the use of children as bone marrow donors is a practice with many ethical implications. The American Academy of Paediatrics’ Committee on Bioethics was concerned enough to develop a policy statement on “children as haematopoietic stem cell donors”.  

According to the committee, the risks of bone marrow donation are small but they do exist: they are mostly to do with the anaesthesia used when extracting bone marrow, but there can also be “nerve, bone or tissue injury”, infection, and transfusion reaction. A number of short-term and some long-term problems are described, including pain at the donation site and bleeding problems. There is also a very tiny risk of death -- one per 10,000 donations. Parents who must make such decisions are conflicted between the desire to have their seriously ill child recover and the knowledge that they are subjecting their healthy child to pain, and some risks, however small. The committee advocates that a “donor advocate” and a child mental health professional or an ethics consultant should be involved in the process.  

These are issues worth discussing when publicising bone marrow transplants among siblings. Are procedures in place to ensure that parents give their consent on behalf of their child, after being apprised of these risks? Are small children asked for their assent before donating bone marrow to a sibling? Are clinical ethics committees consulted in such cases?
 
Incidentally, the World Marrow Donor Association’s minimum age for unrelated bone marrow donation is 18, or the age of consent. There does not seem to be any minimum age for related donation. This is all the more reason to ensure that guidelines to protect donors are followed. 

In India, a one-year-old child has ‘donated’ his bone marrow to a sibling.  

Ethical issues in sibling cord blood transfusions 

Also in the Bangalore hospital, a four-year-old boy with Fanconi’s anaemia, another genetic disorder of the blood, is waiting for the birth of his sibling in order to receive a transfusion of the infant’s umbilical cord blood, considered a particularly good source of stem cells. And in September last year, a cord blood stem cell bank in Chennai got good coverage for its announcement that it had conducted “India’s first successful stem cell transplant using a sibling’s cord blood cells”.  

The recipient in Chennai was an eight-year-old child with thalassemia. According to the article posted on the company’s website, the parents were asked to “consider another pregnancy and go for umbilical cord blood stem cell banking”. A pre-natal test “confirmed that the foetus was not affected with thalassemia,” and when the baby was born its cord blood cells were transfused into the older sibling. But it turned out that the baby’s cord blood cells were insufficient, and were supplemented with bone marrow cells extracted from the one-year-old baby. There was no mention of what it meant for a very small child to be subjected to this painful and possibly risky medical procedure.  

Though the cord blood transfusion didn’t work for the child in Chennai, assuming that cord blood transfusions will eventually become established in India, we should anticipate another concern: the possibility that our medical profession will promote the creation of ‘saviour siblings’ -- babies whose cord blood and, if necessary, bone marrow, is used for stem cell therapy. In such circumstances, assisted reproductive technologists can bypass pre-natal testing altogether. Embryos produced for IVF can be tested to rule out certain disabilities as well as to identify those with a genetic match to the child that needs stem cells. This is the subject of a recent film, My Sister’s Keeper. Pre-implantational genetic diagnosis to select against disability is legal in India and can easily be used to select a match for donation of organs.

Such saviour siblings are apparently already being created in India. The Indian assisted reproductive technology (ART) industry has shown that it is quick to pick up on and promote what the market demands. Look at our surrogacy camps. 

Is the creation of a saviour sibling a good or a bad thing? Is there something wrong about creating a child expressly to save another? What is the ethical basis for organ donation by a minor? How does one conclude that a child wishes to donate to its sibling? Is a child able to consent to such donations? Is there a benefit to the family that outweighs the risk of such practices? We certainly need to discuss such issues. We have the technology, and are certain to use it -- we should be anticipating such concerns and thinking of how to respond. 
 
Bio-insurance: Exploiting the fears of pregnant women 

A different set of ethical questions is posed by the practices of umbilical cord blood banks that collect the umbilical cord at the time of a baby’s birth. The Bangalore and Chennai stories gave plenty of publicity to the two cord blood banks involved. These banks make money by aggressively marketing ‘biological insurance’ -- store your baby’s cord blood with us and if your child happens to fall ill with some terrible disease, the stored stem cells could be used to develop a treatment.  

Pamphlets describing the services and tariffs of these banks are available in the waiting rooms of some gynaecologists’ offices. Pay between Rs 60,000 and Rs 120,000 and store your baby’s umbilical cord blood cells for 21 years. Check out the discounted packages to “accommodate stem cell banking in the common man’s budget”. Pay in easy monthly instalments. Some companies make big promises: if you store your baby’s stem cells with them, “your child and family can (have) access to potential treatments for over 75 serious ailments such as leukaemia (blood cancer), thalassemia, brain injury, juvenile diabetes and many more”. 

Professional organisations in India should be commenting on the science and ethics of such practices. But the websites of the Indian Academy of Paediatrics and the Federation of Obstetrics and Gynaecology Societies of India have nothing on stem cells. However, the guidelines for stem cell research and therapy published by the Department of Biotechnology and the Indian Council of Medical Research require that those running cord blood banks inform parents that “at present the use of stored umbilical cord blood for self is practically nil”.  

The American Academy of Paediatrics (AAP) trashes the notion of cord blood as “biological insurance”; the chances are remote that a child will develop a health problem that can be treated with its own cord blood. The AAP mentions two situations in which cord blood might be stored: directed donation, when a sibling has a medical condition that can be treated with cord blood transplantation, and in a public bank for use by anyone who might need it, as in a regular blood bank, for certain established uses.  

But the private cord blood cell bank in Bangalore conveys the message, in not so subtle terms, that only private banking can assure you of the cord blood should your child need it in the future -- implying that your own cord blood could actually be of use to you. 

The AAP tells physicians to “be aware of the unsubstantiated claims of private cord blood banks made to future parents that promise to insure infants or family members against serious illnesses in the future by use of the stem cells contained in cord blood”. It also notes that “families may be vulnerable to the emotional effects of marketing for cord blood banking at the time of birth of a child and may look to their physicians for advice”.  

Such warnings don’t seem to matter to many doctors in India who seem to actually mediate between pregnant women and cord blood banks by stocking pamphlets for these banks. And companies have no qualms about running ante-natal workshops where expectant couples are educated on “the benefit of cord blood stem cell banking”. 

I must add that not all doctors support the promotional methods of cord blood cell banks. I was alerted to this practice when an obstetrician-gynaecologist called me to complain that a bank tried to distribute its leaflets in his waiting room. He was outraged that someone could exploit the fears of a pregnant woman at her most vulnerable. 

The corporate sector in stem cell banking 

Even if stem cell therapies are in the early stages of research, their potential has drawn the interest of speculators. By 2010, the umbilical cord blood banking business in India is apparently expected to reach anywhere between Rs 140 crore and Rs 2,700 crore -- it depends on who’s being quoted. Already, at least four big players have moved into the market.  

The corporate health sector’s interest in cord blood banks should make us sit up and think. Cord blood in India and China is apparently being viewed as a commodity, the need for which is anticipated in future stem cell research and therapy. Since cord blood is unlikely to be of personal use, the chances are that such banks will cater to people from other countries seeking stem cell procedures. When combined with our trained human power and infrastructure, stem cell tourism may be the new medical tourism. For example, a tripartite venture between an international organisation, a corporate hospital and a drug company has announced that it plans to “build an inventory of 25,000 ethnically diverse units here to help treat critically ill patients in India and abroad”. It must be presumed that the “ethnically diverse units” in this and other banks will serve an international demand for stem cells, with the corporate hospital partner conducting the stem cell procedures.  

In April 2010, an amendment in the Drugs and Cosmetics Act laid down standards for cord blood cell banks which are approved by the Drugs Controller General of India (DCGI). More detailed regulations are being discussed that spell out requirements for these banks, for storage and transportation of stem cells and for their release. While such standards are welcome, they may be motivated more by a need to meet international standards towards India’s medical tourism policy.  

Menstrual blood banks are in the future. As the director of one of the larger cord blood banks told a business journal in March this year: “Menstrual blood banking has the potential to expand our revenue stream multi-fold considering that our total market would no longer be 2% of the population, which represents pregnant women, but almost every woman in the country.”  

The Wild West of stem cell ‘therapies’

If corporate cord blood cell banks see big profits in stem cells as a commodity in themselves, dozens of clinics -- and some big hospitals too -- promise miracle stem cell cures for diseases where conventional medical treatments have failed, using procedures that are untested for safety and efficacy.

In June 2009, a corporate hospital conducted “brain stem cell transplant surgery” on a woman with brain damage. It reported that after the surgery the woman was conscious and able to communicate and move her limbs. The chief neurosurgeon, who is also vice-chairman of the hospital, is quoted as having said: “To our knowledge such attempts were made only in China. This is the first attempt in the country, and India is the second country in the world to use such therapy.” Another hospital representative stated that they were looking at bringing out stem cells as a “product” by 2011.

We’ve heard from many such clinics in recent years, treating conditions where nothing else has worked. The website of one clinic takes care to state that all the procedures that it offers are “experimental therapy” and are approved by an ethics committee. But it does not carry any details on this committee. It claims to follow ICMR guidelines for stem cell research and therapy. These clinics also solicit email enquiries while asserting that they are not legally liable. None of these feats is published in credible medical journals.

One of the better known of this ilk is an in-vitro fertilisation (IVF) doctor who claims to have used embryonic stem cell procedures to cure more than 600 patients with conditions such as Alzheimer’s, multiple sclerosis, renal failure, cerebral palsy, and diabetes. Her patients include politicians and her first press conference was attended by the Union health secretary, the prime minister’s wife, and a former chief minister. She has been written about in the media, but her work has not been subjected to scrutiny by her peers.  

No one knows how much the placebo effect is responsible for some feeling better after such procedures -- or how many have been harmed by them. The only way we’d know that is with systematic research that documents all aspects of the procedure, measures all reported benefits as well as side-effects, and is published. But such doctors deliberately refuse to submit their work to the rigorous demands of formal research. 

This unregulated industry in stem cell procedures, described sometimes as ‘research’ and sometimes as ‘therapy’, thrives in the absence of any serious efforts at regulation. It feeds off the desperation of people with serious illnesses and for whom established treatments have failed, and who might feel that they have nothing to lose in trying an untested procedure.
  
But these procedures may also be unsafe, and the side-effects could be serious, even lethal. There are at least two documented instances of patients developing tumours after undergoing stem cell procedures. But such information can come only from systematic research.  

And of course they cost large amounts of money; desperate patients are willing to pay for any hope of a cure.  

Guidelines and a law

This spectrum of unethical practices is possible because the various guidelines and regulations governing the practice of stem cell research and therapy in India are neither comprehensive nor enforceable.  

The DBT/ICMR’s 2007 guidelines apply to all stem cell therapy and research. They state that all stem cell therapy other than bone marrow transplantation for certain accepted indications is considered experimental. They call for a national apex committee for stem cell research and therapy. All centres doing stem cell research should have an institutional committee registered with the national committee. Stem cell research may be conducted only after review by the scientific committee and an ethics review committee. Stem cell research towards a marketable product must also get approval from the Drugs Controller General of India. A committee should monitor the trial and conduct site visits when required.  

But these are only guidelines. So clinics and hospitals across the country can advertise and offer stem cell ‘cures’ without fear.  

All medical professionals are expected to abide by the Medical Council of India’s Code of Medical Ethics. The Code of Medical Ethics requires that all research abide by ICMR guidelines for biomedical research. At present, almost all stem cell procedures are in the research stage, and embryonic stem cell therapy is not accepted as standard treatment anywhere in the world. So, for example, the IVF specialist who is actually conducting embryonic stem cell research -- of unknown scientific value -- is committing unethical medical practice in the guise of therapy.  

The less said about the code and its enforcers, the better. 

Centres conducting embryonic stem cell research are legally required to get clearance from the national apex committee. That national apex committee has been constituted, but a government order has not yet been issued for it to function, according to Dr Vasantha Muthuswamy, former senior deputy director general of ICMR who was responsible for developing the ICMR ethical guidelines for biomedical research. This allows the IVF specialist to conduct embryonic stem cell procedures, which are actually research, calling it therapy, without fear of punishment. 

At present, only stem cell research towards developing a drug must be approved by the Drugs Controller General of India. In order to give its approval, the DCGI requires evidence that the research is scientifically valid, documents on the trial design and previous data on the safety and efficacy, and review by an ethics committee.  

The DCGI approves cord blood banks as they deal in a product, just as blood banks do. But procedures using stem cells are not treated as drugs and are not covered by the Drugs and Cosmetics Act. So stem cells can be used without proof of safety or efficacy. Stem cells should be categorised as biological products, such as blood products and vaccines, according to Dr Muthuswamy. This would bring all research on stem cells under the purview of the law. This should happen under the National Drug Authority (NDA), an autonomous body which is meant to regulate drugs, devices and biological products. The NDA has been formed but is yet to become fully functional.

The 2007 guidelines are included in ICMR’s draft law to regulate biomedical research. This Bill has been pending for some years. 

A comprehensive and effective regulatory structure that takes into account questions of scientific and ethical practice is urgently needed to put a stop to the malpractices conducted in the name of stem cell therapy. 

(Note: Names of doctors, hospitals and companies have been deliberately left out -- not because the writer feels they are unfairly accused, but to avoid giving them more free publicity)  

(Sandhya Srinivasan is a freelance journalist specialising in public health and development issues. She has a Master's in public health and is Executive Editor of the Indian Journal of Medical Ethics. She was a Panos Reproductive Health Media Fellow in 1998 and an Ashoka Fellow. She is Consulting Editor, Public Health, for www.infochangeindia.org)

Infochange News & Features, December 2010