Long post. Pdf version
Tass & other outlets have reported the story this week about NGO’s collecting Russian human tissue and a US Air force contract tender from July 2017. This blog post will focus on informed consent and processing of human tissue, some ethical & legislative notes and case studies. The full details of this story are not published but with the information available, I believe it breaks the Nuremberg code and every code of practice on informed consent both in human tissue procurement and in clinical research good practice. I don’t know exactly what actions are open to Russian civilians and government but will try and explain my views below. I have worked in a non-clinical role at MHRA, NIHR in the UK so don’t have expertise but potentially know where to look for relevant information. Opinions are personal.
I’m not experienced but from what I’ve read, it could be considered an international crime as in ICC Rome Statute Article 7 – Crimes against Humanity ‘other inhumane actions’ and Article 8 War Crimes ‘biological experiments’1. Is a military option acceptable to either destroy the human tissue which was illegally obtained or get it back, or are there other legal options? I wouldn’t know but fwiw:
Codes of Conduct and Practice
It is 70th anniversary of Nuremberg Code as detailed in an excellent post from CostofLiving project blog. In particular:
The voluntary consent of the human subject is essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved, as to enable him to make an understanding and enlightened decision. This latter element requires that, before the acceptance of an affirmative decision by the experimental subject, there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person, which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility, which may not be delegated to another with impunity.
The experiment should and responsibility which may not be delegated to another with impunity.
The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.2
There is no getting away from the horrific events which led to the development of the code and yet unethical experiments continue and so-called ethical research involves use of e.g. human tissue or data for purposes other than what is was intended. Which invalidates informed consent and there are legal mechanisms available. I don’t know very much about how Rospotrebnadzor regulate human tissue in research and consent (because my Russian isn’t good enough yet), for example whether in Russia there is a mechanism at federal or regional level for automatic opt in / opt out.
In the UK we have the Human Tissue Authority which regulates the usage of human tissue, they are a kind of cousin of Medicines and Healthcare Products Regulatory Agency (MHRA) and work closely with National Institute of Health Research (NIHR). There is a code of practice which must be followed and their remit (defined in Human Tissue Act 2004) includes
There are four fundamental guiding principles which if this had happened in the UK would have been broken – consent, dignity, openness and honesty. Some extracts
The HT Act and common law establish the principle that the decision to consent rests first and foremost with the person whose body, organ, tissues or cells are being used.
Where a person with capacity has made the decision not to consent to an activity covered by the HT Act, then the activity must not proceed as there is no consent in place.
Consent under the HT Act relates to the purposes for which relevant material might be removed, stored or used.
For consent to be valid it must be given voluntarily, by an appropriately informed person who has the capacity to agree to the activity in question. The person should understand what the activity involves, any reasonable or variant treatment and, where appropriate, what the material risks are. The test of materiality is ‘whether, in the circumstances of the particular case, a reasonable person in the patient’s position would be likely to attach significance to the risk, or the doctor is or should reasonably be aware that the particular patient would be likely to attach a significance to it’. Consent may be specific or it may be broader in its scope, sometimes referred to as ‘generic consent’.
Specific consent is given in relation to a defined project, treatment and/or use. Generic consent refers to a broader permission, where consent may, for example, be given to allow the storage and use of tissue for an as yet unknown research project. In practical terms, specific and generic consent may be sought at the same time, to derive the greatest benefit from valuable human tissue donated for research. While obtaining broad or generic consent offers the widest benefit for future research, the seeking of such consent should be supported by safeguards and assurances for donors. For example, if a donor expresses objections to specific types of research, these must be respected, and donors should be provided with information about how future research will be approved within the scope of the consent they have given.
A donation may not proceed if a donor places conditions on their consent which cannot be met or guaranteed.
Further information about conditions on consent can be found in paragraphs 45-48 of this code. Further guidance on consent to research is included in the Code of Practice on Research (Code E).
To ensure that consent is properly informed, commercial organisations offering services related to the removal, storage and use of human tissue and cells must ensure that materials provided to customers to aid their decision-making, such as marketing and advertising materials, are accurate and abide by the Advertising Standards Agency’s guidelines.
Non-commercial organisations must also ensure that materials provided to individuals to aid their decision-making are accurate.
The HT Act does not prevent an individual from placing limits on their consent via the imposition of conditions, for example, to particular research studies or to donate specific organs. The HT Act recognises that individuals have the autonomous right to give or refuse consent to the use of relevant material for scheduled purposes. Consent may differ in its duration. It may be enduring or time-limited. Enduring consent means that it remains in force unless consent is withdrawn. Consent may be withdrawn at any time, whether it is generic or specific. Withdrawal should be discussed at the outset when consent is being sought. The practicalities of withdrawing consent and the implications of doing so should be made clear. 3
And re living persons consent
Under the HT Act, consent is needed for storage and use of tissue from a living person for the following scheduled purposes including
a) obtaining scientific or medical information which may be relevant to any person including a future person;
b) public display;
c) research in connection with disorders, or the functioning, of the human body;
Tissue may be taken in a variety of circumstances, for example:
a) in the course of diagnostic procedures, such as taking a blood or urine sample, tissue biopsy, cervical screening;
b) in the course of treatment, such as removing tissue (organs, tumours) during surgery; and
c) when removed specifically for the purpose of research
To give consent, the individual should understand the nature and purpose of what is proposed and be able to make an informed decision. They should be told of any material or significant risks inherent in the way the sample will be obtained, how the tissue will be used and any possible risks or implications of its use, such as genetic tests. The test of materiality is set out in paragraph 40. If the person concerned is not a patient, and is volunteering samples purely for research, the general principles of providing appropriate information still apply.
Establishments meeting these Standards will be able to demonstrate full traceability for the human material for which they are responsible, from receipt to final disposal/disposition. HTA inspectors will test this through traceability audits carried out on site and we expect establishments to take a pro-active approach to assuring themselves of effective traceability throughout the lifetime of their licence. 4
If there is uncertainty about the reasons for the donation e.g. for security reasons related to the US Air Force then informed consent is not possible. At all. There’s no way it happened in this case – going through the motions of an informed consent for a specified procedure by a military entity – they have totally abandoned the bioethical principles which led to the development of the Nuremberg code and other codes of conduct. So the tissue cannot be donated because the persons concerned don’t know how it will be used even if generic consent has been ‘said to be obtained’. The only way I think this could be verified is if the UN and also if Russian military & government entities had unlimited access to the sites where the US Air force is using the tissue ! This would fit with internationally agreed standards for clinical practice in research but not likely in my lifetime I guess.
Had they chosen to perform this research by working with Russians – asking Russian entities to complete the donation & consent and use it at a Russian facility in Russia, then it would be different. But they did not do this and it is very unlikely that an NGO carrying out the donation collection would know the intended purposes (regardless of what is in the tender documents) so cannot provide an informed consent in a way that a Russian based suitable entity could. It would also be more sensible regarding storage, reuse and disposal so that it could be appropriately regulated via Rospotrebnadzor & Duma legislation (with any appropriate presidential input of which I understand little more than nothing yet).
By choosing to publish an opportunity on a website with very little detail, then dignity has also been violated. Honesty and openness are not possible if it’s being co-ordinated by a military entity, especially a foreign military entity that is making use of the human tissue outside of Russia.
In ICH Good Clinical Practice for research trials, some extracts regarding consent and coercion which are relevant:
In obtaining and documenting informed consent, the investigator should comply with the applicable regulatory requirement(s), and should adhere to GCP and to the ethical principles that have their origin in the Declaration of Helsinki.
Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate or to continue to participate in a trial. Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include explanations
(a) That the trial involves research
(b) The purpose of the trial
(f) Those aspects of the trial that are experimental
(h) The reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be made aware of this. 5
I don’t know of a specific precedent other than international cases brought forward at Nuremberg, or others which led to the Declaration of Helsinki.
A foreign case which is currently dealing with the removal of tissue from deceased persons without informed consent is that of the Ivano-Frankovsk regional morgue in western Ukraine, where it is alleged that parts from 56 human corpses were improperly fed into the international tissue market.8 In 2012, charges were filed against the morgue’s deputy director, three coroners and a nurse alleging that they deceived families into signing consent forms and that they did not get proper permission before tissue was obtained from corpses. These latest criminal charges in Ukraine follow an investigation published in July by the International Consortium of Investigative Journalists (ICIJ). The ICIJ probe revealed legal, ethical and medical concerns surrounding the growing for-profit human tissue industry. Families told the ICIJ that their relatives’ cadavers were harvested without informed consent. 6
Washington University v. Catalona. Dr Catalona had argued unsuccessfully in the lower courts that research participants who donated tissue and blood samples to the university for prostate cancer research could require the university to transfer their tissues to him at his new place of employment.15 The Court upheld a unanimous 2007 ruling by the Eighth US Circuit Court of Appeals that stated prostate tissue and serum samples donated to Washington University may continue to be used by the institution for cancer research.
The appellate court had affirmed the lower federal district court ruling that donors who gave tissue or serum samples to the university for research cannot later compel the school to transfer ownership of the samples to another research institution. The Court held that under the specific facts of the case, the men who participated had donated their tissue to the university as a gift and they could not get it back or have it sent to another researcher. However, the Eighth Circuit Court indicated that the men retained the right to stop participating in the research by:
• declining to answer any additional questions
• not donating more tissue, or
• disallowing the use of their tissue in future research.
This means that the men have the right to order the university to stop using their tissue, and the university cannot merely strip their names off it and continue to use it as they please.
Moore v Regents of the University of California, the physician treating Mr Moore for hairy-cell leukaemia in 1976 removed samples of his blood, bone marrow aspirate and other tissues and fluid for examination.17 The physician and his research assistant knew upon taking these samples that the tissues had potential commercial and scientific value as material for medical research, but they did not disclose this information to Moore.17 In 1979, the University of California, Los Angeles (UCLA) Medical Center researchers established and patented a cell line from Moore’s cells. The patent was assigned to the Regents of the University of California (Regents) who assisted the researchers in commercial development of the cell line and products to be developed from it. When Moore discovered that his cells had been used in developing the patent, he took legal action against Regents and the UCLA Medical Centre researchers and doctors involved in his care.
The California Supreme Court found that Moore had a cause of action for breach of his physician’s disclosure obligations and that an individual has a tangible property right in his or her own tissue. 18 In dicta, however, the court explicitly stated that its decision left undecided whether the transfer of human tissue should be gift-based or market-based, and that future controversies would have to be decided on a case-by- case basis. 7
R v. Kelly.23 In this case, a technician who worked at the Royal College of Surgeons removed body parts and gave these to an artist who used the body parts as moulds to create sculptures. Both the technician and the artist were subsequently charged with theft. They argued that parts of corpses are not property and could therefore not be stolen under the British Theft Act. The Court of Appeal held that parts of a corpse are capable of being stolen, if they have acquired different attributes by virtue of the application of skill. As the body parts in question had been preserved and used as specimens, they became fit for proprietary rights. 8
Medical practitioners at St Augustine’s Hospital performed 109 illegal operations between 2001 and 2003, which included the removal of kidneys from five children, and admitted receiving R3.8 million from an illegal organ-trafficking syndicate. Legal requirements relating to informed consent in the South African medico-legal context have been discussed extensively.25 In the context of medical research, specifically Section 12(2) (c) of the Constitution of the Republic of South Africa, 1996, states that everyone has the right to bodily and psychological integrity, which includes the right not to be subjected to medical research or scientific experiments without his or her informed consent. 9
No. 750000/08. The plaintiffs, the next of kin of the decedents alleged the following causes of action by way of master complaints, which listed the following counts: Count I. Negligence; Count; II. Negligence against defendant funeral homes; Count III. Negligence against, the tissue processors; Count IV. Negligent Infliction of Emotional Distress; Count V. Intentional and Reckless Infliction of Emotional Distress; Count VI. Intentional and Reckless Infliction of Emotional Distress; Count VII. Intentional and Reckless Infliction of Emotional Distress; Count VIII. Negligent Misrepresentation; Count IX. Violation of the New York Consumer Protection Statute, N.Y. Gen. Bus. Law § 349; Count X. Loss of Consortium; Count XI. Loss of Sepulcher against all defendants.
The court’s holding – that the guidelines of the AATB (American Association of Tissue Banks) are greater than those required by state or federal statute and the corresponding state and federal regulations as memorialized in the contractual amendments between the parties. Therefore, the plaintiffs’ master complaint has set forth a prima facie case for interference with the right of sepulcher. The moving defendants’ motion for summary judgment dismissing the plaintiffs’ cause of action for loss of sepulcher is denied. While this court finds that the defendants, owed the plaintiffs in these coordinated actions a duty not to interfere with the remains of their deceased family members, they move in the alternative to dismiss those claims that are duplicative of the plaintiffs’ interference with the right of sepulcher claims. The Appellate Division, First Department citing the Court of Appeals decision in Murphy v. American Home Prods. Corp.26 held that “․ a cause of action for infliction of emotional distress is not allowed if essentially duplicative of tort or contract causes of action.”27 Here, the outrageous conduct complained of by the plaintiffs is an essential element of a claim for interference with the right of sepulcher.28 Furthermore, each tort seeks duplicative recovery for psychological injuries.
Accordingly, this court finds that the plaintiffs’ claims for Negligence (Counts I, II, III and VIII) the Negligent Infliction of Emotional Distress (Count IV), Intentional and Reckless Infliction of Emotional Distress (Count V, VI and VII) are duplicative to the loss of sepulcher claims and thereby dismisses those claims. Tutogen Medical was not a party to the contract and is hereby dismissed as to all counts. 10
These are just small examples relating to ownership.
Other references to articles, cases
In ‘Tissue tug-of-war’ it states
that only a limited number of cases in the United States have addressed the issue of whether a patient or research subject retains any right to his tissue once it has been removed at a doctor’s office or hospital.The issues that arise in the context of tissue rights, namely ownership, informed consent, patient autonomy, and a patient’s right to withdraw, have otherwise remained mostly untouched by the United States courts and state and federal legislatures. The federal regulations governing the collection of human-subject tissues for research provide guidance as to informed consent, but leave many questions unanswered regarding a subject’s right to withdraw or otherwise control her tissue samples after the samples are taken.
The United States comprehensively regulates informed consent, and a patient must be informed of his right to withdraw from scientific research. (234) However, this informed consent loses its value if the right to withdraw is restricted merely to refusing to give additional tissue samples to the research; the full right to withdraw or destroy the already excised tissue sample itself is necessary to provide individuals with the self-determination they deserve.
Anonymization of a tissue sample is simply insufficient to fully protect a patient’s interests. There are three reasons why de-identification does not accomplish anonymity of the tissue. First, “anonymizing” tissue is a misleading term because although the anonymization process requires that the patient’s name and identity no longer be linked with the sample, it cannot ever fully strip the tissue of its connection to the person from whom it was taken. (235) The tissue contains the individual’s unique DNA, the most basic level of human identity. As science and technology progress and scientists understand more about the details of each person’s specific DNA strains, DNA will likely become even more closely identified with human identity.
Second, anonymization is insufficient as a solution to a patient’s wish to withdraw his tissue sample because the patient’s family members will be unable to have further access to the tissues once they are anonymized. 11
Whatever the FDA and Congress decide regarding revisions of their current legislation about informed consent, they should be leading in condemning the way that this has been carried out in violation of humane rights of any citizen regardless of any political or personal feelings towards any Russians, regardless of media madness and political / military maneouvering.
Or what was the point of Nuremberg Code and the thousands of hours of input into bioethical guidelines, the thousands of health professionals who have to make judgements and help guide people to the best decision regarding research?
Or are we not human anymore and we just don’t care?