10:33 AM Mar 11, 1997

THE TRADE IN HUMAN TISSUE

Geneva, 10 Mar (TWN/RAFI) -- Just about two centuries ago, trade in human body (slaves) was outlawed, and bans have been written into several national constitutions and international instruments.

But there is now a large and growing South to North and North to North movement of human tissue, catering currently to an annual $428 million market which could grow into a $80 billion a year of trade in human tissue culture products.

This trade is taking place in a total policy and regulatory vacuum, with very serious public and policy implications and there is a need for the UN High Commissioner for Human Rights, the International Court of Justice and the UN General Assembly to play a role in addressing these issues, says the Canada-based international NGO, the Rural Advancement Foundation International.

The culture and study of human tissues with genomic technologies promises major medical breakthroughs; but also presents profound, unaddressed international policy and ethical concerns. The global trade in human tissue - especially that of rural populations and indigenous peoples - has expanded dramatically in recent years and has far outstripped efforts to create policy mechanisms to ensure the rights of tissue donors. The tissue trade is the foundation of a burgeoning industry that depends on patenting and selling pieces of the human body and gathering and providing access to proprietary genomic information.

Few, if any, people and organisations have a handle on the ethical and legal implications of the rapidly expanding tissue traffic. This gap in international policy must be quickly addressed by appropriate multilateral bodies and professional organizations if rights of patients and research subjects are to be enforced.

Tissue culture is the reproduction of micro-organism, plant, and animal cells in the laboratory. The culture of human cells is crucial for the biotechnology industry. When kept under proper conditions, 'immortalized' human cell lines can reproduce in perpetuity and provide an infinite quantity of cells that contain the unique DNA of the original tissue donor. Valuable human tissues also include simple frozen tissue samples (usually blood) which, when preserved correctly, retain DNA and proteins which can stored, tested, and sequenced, and whose properties can be recorded in computer databases and called up (or thawed out) in the future.

Using gene sequencing equipment and electronic communications, scientists can even create a set of instructions for producing unique bits of DNA found in a given tissue sample, send those instructions around the world, and have a colleague synthesize the DNA of interest in a remote location.

But the new technologies have not supplanted the need for human tissues to be physically interchanged. In fact such technologies and the intellectual property systems that permit the monopolization of human tissue combine to form a powerful industry whose existence depends on the exchange and sale of human tissue, tissue products and equipment for growing it.

Either through their own efforts, or through alliances with other biotechnology companies, major pharmaceutical transnationals are moving to secure a place in the tissue culture industry.

According to the US consulting firm, Frost and Sullivan, the worldwide market for cell lines and tissue cultures brought in $427 million in corporate revenues in 1996... (and) the market will grow at an average annual rate of 13.5% over the next seven years and may be worth $914 million by year 2002.

Products from cultured tissues are worth considerably more. For e.g., Genentech, a US company which is majority owned by Switzerland's Roche, uses cell culture to make 'Activase', a blood-clot dissolving drug administered to persons who have recently suffered heart attacks. Activase is made by a hamster ovary cell line modified with human DNA that has been spliced into the hamster cells from a human melanoma cell line. Activase rakes in $200 million in sales a year.

Blood cells from the umbilical cords of newborn infants, which have potential therapeutic applications later in life, are now stored - for a fee - by several companies. Meanwhile, in Europe and the US, health authorities, patent offices, doctors, activists, and companies fight over who should profit from this business and how?

One internet directory of tissue culture-related enterprises, currently lists 38 companies in the US alone which specialize in selling cells, cell products and tools for cell culture. Some have internet home pages where customers can peruse online catalogues of 'normal' and/or 'mutant' human tissues for sale.

According to Frost and Sullivan, the human tissue industry has a marketing problem. Its companies have a hard time differentiating their cell lines from those sold by other companies. As a Frost and Sullivan press release puts it, "The users of cell culture products view them as commodity items for which there is no difference between vendors and products." Frost and Sullivan says that industry is moving to emphasize product differentiation in order to bolster human tissue prices. It seems likely that companies will seek even more patent protection for their human tissue products and processes in an effort to set themselves apart and monopolize pieces of the growing market.

An unfortunate reality, currently confronts the enormous number of people who, for clinical or research purposes, give blood or other samples of their tissue. They may unwittingly become a statistic in the international human tissue trade - in some cases even if the tissue donor simply gave blood for a blood bank. Donors' cells may be frozen, and/or immortalized and shipped across town, across the world, or both. Genetic profile information from analysis of the cells - directly, partly, or unrelated to the purposes for which they were collected - may be created and placed in a database available to thousands.

For instance, whole blood samples given by persons with unusual blood characteristics who register to be bone marrow or platelet donors at a Red Cross centre in rural Japan are distributed internationally for research purposes. Recipients include the University of California at Los Angeles (US) and the Canadian Red Cross. The ultimate disposition of these samples at their international destinations - whether they were immortalized, used and discarded, stored or further distributed -is unclear.

In many places, especially in the North, human tissue is banked. Well-known human tissue collections include those at the US American Type Culture Collection (ATCC) and the European Collection of Animal Cell Cultures (ECACC) in Porton Down, UK. Other, less-well known collections exist that have thousands of blood samples and cell lines from people across the globe and with varying levels of documentation of their origin.

In the US, for e.g., more than 250,000 sex offenders and other criminals have been sampled. The US military expects to have collected and stored more than 3 million blood samples of its own troops by 2001. Several US states have saved collections of over 1 million blood spot cards (called Guthrie Cards) collected from newborns.

In Colombia, the Genetic Institute of the Universidad Jnaveriana in Bogota, has an enormous collection of tissue samples from Colombian indigenous people. It sent 2305 blood samples to the US National Institutes of Health laboratory which 'invented' the Hagahai cell line that was patented by the US Government.

The Coriell Institute, a US non-profit research organization and tissue bank, distributes cell lines from diverse peoples and places, including: Karitiana and Surui (Brazil), Biaka (Central African Republic), Huaorani (Ecuador), Mayan (Mexico), Maori (New Zealand), Quechua (Peru), Bougainville (Papua new Guinea), Pima, Pueblo and Cheyenne (all US), and Mbuti (Zaire). A researcher who is just interested in DNA (as opposed to cell lines) can order the "Human Diversity Collection DNA Pool", which consists of "Pooled DNA samples consisting of equal quantities of DNA from 13 males and 13 females from the following populations: Mayan Indian, Karitiana India, Suri Indian, Quechua India, Auca Indian, Jemez Pueblo Indian, Cheyenne Indian, Khmer Cambodian, Southern Chinese, Japanese, Druze Arab, Nasioi Melenaesian, Biaka Pygmy, and Mbuti Pygmy. Two individuals from each of the populations were selected for the pool.

Researchers who receive Coriell cells must pledge not to share them with third parties or patent them.

But it isn't always the case that such pledges are requested by tissue banks distributing large quantities of human tissues. The Human Biological Data Interchange (HBDI), a US government-funded tissue bank for diabetes research in Pennsylvania (US) advertises 'availability for immediate distribution... cell lines and DNA from 385 families with diabetic and unaffected siblings." The cell lines include "pedigrees" (multiple cells lines from various members of a family) from the US, Swedish, Italian, and Dutch people as well as "Bedouin Israeli" and possibly Colombian indigenous people. The number of cell lines banked per family varies widely, from just 2 or 3 up to 86. In some cases HBDI offers to contract with interested researchers for the custom collection of additional samples. HBDI makes no effort to restrict patenting of cell lines in the collection (or products of cell lines). Instead, HBDI sidesteps the issue, saying "HBDI has made no attempt to determine outstanding rights on the cell cultures or other matter in the HBDI repository. HBDI disclaims any knowledge relating to property interest in the human biomaterials provided" and goes on to refer potential patent seekers to the source family of cell lines.

Possibly, the most extensive organized effort currently underway collecting, characterizing, and distributing human tissue is the International Histocompatibility Workshop (IHW), a loosely-organized group of scientists of different specialities who focus their study on a region of the human genome known as the Major Histocompatibility Complex (MHC).

For its 12th meeting, which took place in France in June 1996, the IHW gathered information on over 26,000 human tissue samples collected by participating laboratories. 366 of these samples were immortalized into cell lines and distributed as a group (called a 'cell panel') at the meeting in France.... The IHW's cell panel manager is the ECAAC, which invited IHW participants to order the entire panel, or just parts of it. The cell lines are now part of ECACC's permanent collection and, like those from the cell panels of previous workshops, can be ordered by interested laboratories.

Although, the terms under which the ECACC distributes these cells are somewhat more restrictive than those used by HBDI, the ECACC does not prohibit researchers from patenting or otherwise commercializing the IHW cell lines. Instead, it requests that any researcher who "wishes to exploit or use any of the cell lines or any progeny of derivatives thereof on a commercial basis... make a formal written request to the ECACC." The ECACC then checks with the lab that deposited the cells - which, importantly, might or might not be the sample collector - to see if commercialization is ok.

Where do the tens of thousands of samples in the human tissue trade come from and for what purposes are they collected?

Samples are rarely, if ever, collected for the specific primary purpose of immortalization and distribution. More often, they are collected through a variety of means including surgery, voluntary participants in disease research, and transplant/transfusion tissue donations. They can also be collected from cadavers. In many cases, research subjects and/or patients may be aware and approve of the reproduction and uses of their cells; but in thousands of cases they may not. For instance:

* Colombian indigenous peoples' cells sent to the US government and corporate researchers were collected as part of the human genetic diversity program by academic researchers. These researchers were operating with grants from the public sector and industry (including pharmaceutical transnationals). Colombian indigenous peoples' leaders say the communities who gave blood understood their donations to be for immediate medical purposes rather than long-term storage and international sharing;

* Residents of the South Atlantic Island of Tristan da Cunha gave blood samples to Canadian academic researchers working on asthma research. The Canadians subsequently passed the tissue samples to a US pharmaceutical company seeking patents on asthma genes. They also accepted a multimillion dollar contribution from another company to build new scientific facilities for human tissue work.

* A cell line was established from US citizen John Moore's body after tissue was removed from his body during surgery. Moore's legal attempts to regain control of the cell line (which was patented by his own doctors) were denied by US courts.

[This is part I of a three-part series, excerpted from the RAFI Communique of January/February 1997, and published in view of its topicality -- meetings of the Human Rights Commission, the preparations in New York for the Rio+5 special session of the UN General Assembly, and WHO's plans for expert consultations and debate on a part of the problem. RAFI is a Canada-based public interest international NGO. Fax 613-567-6884 and email: rafican@rafi.ca]