/ 27 August 2015

Stem cell research outstrips legislation

Stem Cell Research Outstrips Legislation

It starts in a dish: a collection of cells that can be made to grow into corneas, hearts or livers, or used to treat currently incurable diseases. This is the future that stem cell therapies could offer us, but the path to that future is strewn with ethical and legal pitfalls that South Africa needs strong laws and regulations to govern.

“The law has struggled to keep pace with science and medicine,” said Professor Michael Pepper, the director of the Institute for Cellular and Molecular Medicine at the University of Pretoria. “Things move too quickly and the law lags behind.”

Although there are only a few proven stem cell therapy treatments, namely blood stem cell transplants such as bone marrow transplants and skin stem cell grafts, future developments in the field could alter the trajectory of healthcare.

Stem cells are undifferentiated cells that could become any other cell in the human body. This means the same cells could be used to grow heart, liver or any other tissue, and manage or possibly cure many illnesses for which there is no treatment at the moment.

Stem cell usage is governed by the National Health Act 61 of 2003, with the final provisions for the control of human tissues coming into force three years ago.

“There are no official guidelines and standards from the department of health dealing with human tissues,” Pepper told an audience at the launch in Pretoria last week of a special supplement to the South African Journal of Bioethics & Law.

The regulations gazetted in 2012 did not adequately cover cell-based therapies, biobanks (repositories of human biological material and their associated data, specifically used for health research) and transplantation in general, he said.

But Terence Carter, the deputy director general of the department, said this was not strictly true. “There are regulations, but we recognise that the regulations are not adequate to govern the Act … There are weaknesses and deficiencies.”

He said the department had been communicating with experts in the field for nearly a year, and that a workshop was being convened to address gaps in the legislation and regulation.

The establishment of a national oversight body “is part of what we need to do when we change the regulations”, said Carter.

“Clearly this is a major area of development, and we certainly don’t want to be in a position where patients could benefit from stem cell technology but our regulations are out of date and people cannot access whatever technology is available. But this has to be done in a way that is ethically sound.”

Michael Pepper of the Institute for Cellular and Molecular Medicine at the University of Pretoria says we need an external oversight body for the law to keep up with stem-cell science. (Photos: Madelene Cronjé, M&G)

Professor Ames Dhai, the director of the Steve Biko Centre for Bioethics at the University of the Witwatersrand, said South Africa needed clear regulations in the field because “researchers and scientists would actually have an understanding as to the constraints of the law and how far their scope would extend. The other thing is that regulations would also protect the public and the donor of the tissue.”

Dhai, who co-edited the special edition with Pepper, said: “We don’t just need the cold law, but an ethical approach to the law. We need the law to put into regulations the importance of benefit sharing, and the importance of ensuring that participants aren’t exploited, give proper consent and understand what consent entails.”

The dearth of guidelines has led to professional bodies setting up guidelines of their own. South Africa has bodies governing tissue banks (different from biobanks in that tissues are stored there and are not used for research), transplantation, assisted reproductive technology and cell-based therapy, among others.

But a concern raised at the launch of the special supplement was that the regulator might see these organisations’ guidelines as favouring the practitioner rather than the patient.

“There needs to be an external oversight body,” Pepper said. Although these unofficial guidelines were keeping practitioners in line, “there are a lot of bogus stem cell therapies that are appearing throughout the country”.

For a medicine or treatment to be used on a person, it has to be registered with the Medicines Control Council (MCC), reviewed by an ethics committee, be assessed in clinical trials – where it is proven to be effective and safe – and the findings of the trials must be peer-reviewed.

The stem cell research lab at the University of Pretoria.

Marietjie Botes, an expert in medical and biotechnology law, said: “Stem cell [therapies] have a lot of hype and hope. [They] hold the possibility of treating and curing diseases for which no therapy exists … [but] people try to circumvent and fast track the process [to get medicines approved for human use] to try and market the product.”

There are a number of reports of bogus stem cell therapies. For example, between 2002 and 2006, Cape Town-born Steve van Rooyen and Laura Brown allegedly sold stem cell treatments for a variety of chronic diseases for between $10 000 and $32 000. According to the FBI, they “injected each customer in the abdomen with 1.5-million stem cells regardless of their disease”. Van Rooyen is still on the FBI’s most-wanted list for selling their unproved therapy to terminally ill patients.

Scientists in the fields are concerned that South Africa, because of the gaps in its law and regulations, and its inability to enforce existing legislation, is becoming a stem cell “tourism” destination.

Melodie Slabbert, the deputy dean of law at Unisa, who contributed articles to the journal, said: “Stem cell tourism is patients travelling to various destinations to receive stem cell-based ‘treatments’, advertised on [the] internet and social media. They are potentially harmful, unsafe and ineffective.

“If we don’t do something drastic, this will continue to happen, and we will see more of these treatments and bogus operators offering them.”

Repeated attempts to contact members of the MCC to find out from their records whether bogus treatments were on the rise, and what the council was doing about complaints that it had received, were unsuccessful.

The department of health said it had not officially been informed of bogus treatments, which would be investigated, but cases had been reported in the media.

Slabbert said South Africa had a patchwork of legislation, and “it creates the impression that our system is lax and our laws can be exploited, and this is sometimes the case”.

Asked to comment on the state of human tissue legislation for research purposes, the Medical Research Council president, Glenda Gray, said: “There’s been a suggestion that the Medical Research Council and the Academy of Science of South Africa convene a meeting to discuss these issues and come up with recommendations that anyone can use. It is important to regulate all research and therapy using human tissue.”

Biobank presents a conundrum

The genes of Southern Africans, who have some of the highest genetic diversity in the world, could hold the key to prevent or cure many of the diseases ravaging the region and the world.

But research in this field has a difficult line to walk: scientific progress on the one hand, and the threat of exploitation on the other.

Biobanks – repositories of human biological material and their associated data, used for health research – are “a major advance in terms of science and technology”, says Professor Ames Dhai, director of the Steve Biko Centre for Bioethics at the University of the Witwatersrand.

A bank containing hundreds of thousands, possibly even millions, of samples with the donors’ medical and demographic information would allow scientists to conduct research with the possibility of statistically significant results. This could pave the way for personalised medicine tailored to South Africa’s population.

“It allows the opportunity to make new discoveries … [but] it is important that it is regulated to avoid exploitation,” says Glenda Gray, president of the Medical Research Council, although she says that all research conducted in this area would require ethics approval.

Also, “if [South] Africa sets up biobank facilities and has all these rich samples, you have to protect them and ensure that you are not exploited by Big Pharma or other countries”.

At the moment, biobanks are not included in South Africa’s human tissue law, but researchers and policymakers acknowledge that they need to be.

Dhai recognises that there are “unique ethical issues in biobanks research.

“Some of the concerns include issues of individual and group autonomy, informed consent, secondary use of data, data sharing, benefit sharing and differing legal requirements across national boundaries,” she says.

The issue of informed consent is particularly contentious.

“The fundamental issue is the patient’s competency to make the decision [to have their tissue used for research],” says Jacquie Greenberg, a professor of human genetics at the University of Cape Town.

“When I ask a patient for cells, do they know what I am asking for? Do they understand what we are going to do with the sample?”

These questions become even more complicated when the patient or donor’s tissue is stored indefinitely.

There is also the possibility that this tissue could be used in other research, not just the one for which it was originally intended.

“It’s so important to have science and technology, but we cannot ignore an important component of science and technology: the ethical, legal and social issues which go hand-in-hand with [them],” Dhai says.

Blurred lines, loopholes could brew up a storm in a petri dish

After 14 days, a fertilised human egg develops a nervous system. Up until that point that embryo can be used for research and to make embryonic stem cells, which, in turn, can be used to make any of the cells contained in our tissues and organs. To do this needs ministerial approval.

But this is only one way to use, and obtain, stem cells, albeit a controversial one.

“Stem cells are, in the main, not controversial,” says Michael Pepper, director of the Medical Research Council’s extramural research unit for stem cell research and therapy at the University of Pretoria. “Ninety percent of the work done on stem cells is not controversial, but embryonic stem cells are one area that people seem to focus on in the public domain.”

There are two types of stem cells in mammals: those found in the embryo that, if left to divide and develop, will become a fully functioning organism; and adult stem cells, which replenish adult tissues and are found in the bone marrow, skin and fat tissue. Embryonic stem cells are called “pluripotent” because they can become any other cell.

Somatic nuclear cell transfer – the process by which embryos are formed following the fusion of an adult cell with an enucleated egg – is not controversial per se, but raises ethical and legal questions when it is used to produce embryonic stem cells because the embryo must be destroyed to extract the cells.

Reproductive cloning entails the manipulation of genetic material to create a human and is prohibited under South African law. Therapeutic cloning, on the other hand, is legal and involves genetic material from adult, zygotic or embryonic cells being manipulated to alter, for therapeutic purposes, the function of cells or tissues.

“From a legislative point of view, in South Africa the preparation of human embryonic cells and all research involving these cells require ministerial authorisation,” Pepper says.

But the issue of accessing these eggs, or oocytes, is “one of the most important ethical and legal issues associated with somatic nuclear cell transfer”, he says. “We may not trade in [human] eggs.”

It is illegal to pay a woman for her eggs, although she can be paid up to R7 000 in compensation for her time and the potential discomfort.

But while the legislation takes a hard line on this aspect of stem cell research, new developments have created a gaping loophole. In 2006, Japanese scientist Shinya Yamanaka and his colleagues at Kyoto University showed that it is possible to manipulate any cell in the body into becoming a stem cell. This is known as an “induced pluripotent stem cell”.

Although there are laws covering gametes – eggs and sperm, the fusion of which results in a zygote or fertilised egg – there is no legislation governing the use of induced pluripotent stem cells. “How do you regulate this? It is not an egg or sperm, neither is it an embryo,” Pepper says.

There is no doubt, however, that this is the direction research is moving in. “You can take cells from the same individual and put them back into that individual, and they don’t need lifelong immunosuppression therapy,” he says.

Yet, although the techniques used to derive induced pluripotent stem cells are not ethically controversial, “the downstream uses of [these cells] may under certain circumstances be problematic”, says Melodie Slabbert, deputy dean of law at Unisa. For example, it may allow for germline editing, in which inheritable traits passed on from parent to child can be altered.

Many experts are calling for the usage of, and research on, these and other forms of stem cells to be regulated by the health department.