Jul 22
Posted by: nicholasswetenham  

The book I’m reviewing today, The Immortal Life of Henrietta Lacks by Rebecca Skloot, is a bestseller, and deserves its popularity – it is an enthralling story and a fantastic piece of popular science writing, the first time I have seen bioethics presented in such an engaging manner. It tells the story of Henrietta Lacks, who died of a very unusual cancer of the cervix in 1951. Doctors who treated her cancer at Johns Hopkins hospital in Baltimore took a sample of the excised tumour. Cells from this cancer proved to be ‘immortal’ – if kept in the right environment, they reproduce without end. These were the first human-derived immortal cells to be grown succesfully. They were named HeLa after Henrietta, and rapidly spread to laboratories across the world. Without them, many medical and scientific advances of the past 60 years would have been difficult or impossible.

Henrietta and her husband David Lacks, 1945. Copyright Lacks family. Source: Wikimedia Commons.

Henrietta and her husband David Lacks, 1945. Copyright Lacks family. Source: Wikimedia Commons.

At the time, however, informing patients and obtaining their consent before doing this was not required or even commonplace in the US. The cells also proved to have enormous commercial value as they became mass-produced for cell biologists everywhere, but the family only discovered that this had happened decades later, and only by coincidence. Rebecca Skloot’s narrative is divided between historical reconstruction of the lives of Henrietta and her children, and direct accounts of the family’s experiences when Rebecca was researching the story in the early 2000s. Spanning 89 years, the story winds together the threads of research, medical practice, poverty and race. Henrietta’s children experience turmoil as new truths come to light about the way Henrietta and her eldest daughter Elsie were treated by doctors. They also find it difficult to accept that they struggle to obtain medical care because of their income and insurance status, having never received any compensation for the contribution that her cells have made.

Since the books’ publication, there have been some happy developments. In this blog by Nursing student Meg, you can read about the steps Johns Hopkins has taken toward recognising Henrietta’s contribution, nearly 50 years after the fact. A headstone has been placed on Henrietta’s previously unmarked grave. The profits from the book have also been sufficiently healthy to help fund the education of Henrietta’s five grandchildren, meaning that her family at last is gaining something from the story.

In the UK the Human Tissue Act 2004 has considerably strengthened the rights of tissue donors, as I saw firsthand when I had the privilege of learning anatomy by dissection in my first year as a medical student. In the US many issues remain equivocal – in particular, significant commercial gain from one person’s tissues often does not entail compensating them in any way, although the genes and cell lines derived from the them are often patented by individuals or corporations with commercial gain in mind. Thus patent-holders may restrict access to scientific discoveries or demand money for them, but the person from which they are derived often cannot. Thankfully, the current trend international trend in intellectualy property seems to favour the opinion that cells and genes ought not be patented, with all eyes set on Myriad’s patent of the BRCA1 gene for breast cancer. Myriad is set to have its appeal heard in the federal circuit of the US courts. Meanwhile, it remains unclear how to adequately compensate tissue donors for income generated from their samples. 60 years on, the ethical questions raised by Henrietta Lacks are still with us.

Aug 11
Posted by: nicholasswetenham  

Should anyone be penalised for participating in a suicide, which of itself is not a crime? Should doctors be the guardians of life or should they be as Charon, providing passage between the worlds of life and death?

These to me seem to be the two distinct issues at the heart of the modern right-to-die debate and indeed the two that were debated at this year’s British Medical Association’s (BMA) Annual Representatives Meeting. On the first question, the BMA was ambivalent – it did not support a ‘change in the law’ to decriminalise prosecution of assisted suicide. On the second, there was a resounding ‘Guardians of life!’

The court success of Debbie Purdy in the House of Lords (Law Lords branch, which will be revamped as the Supreme Court in October) shows that the answer to these questions is still muddled in English law. The judge’s decision means that assisted suicide may effectively be legalised in the UK in the near future. A Number 10 Petition has been set up in riposte.

UK law is composed of  1. Case or common law (legal precedents set by court decisions which guide future cases) and 2. Statute Law (Acts of the UK Parliament or devolved nation Parliaments/Assemblies). At present suicide is legal under the UK Suicide Act 1961 but assisting it is not, although people who travel abroad to do it in jurisdictions where it is legal have not been prosecuted. The organisation Dignitas in Switzerland has now assisted somewhere in the hundreds of UK citizens in committing suicide, but no parties have been prosecuted. This is the result of court precedents but no statute upholds this as a freedom.

In usual alarmist style, the Daily Mail has published this article about assisted suicide in Oregon. They focus on one case of an unsuccesful assisted suicide. However, the stronger secular case for the current law, some of which are outlined in this FT letter (and then dismissed), are that it protects against the dangers of coercion into suicide by relatives or friends, a feeling that one is a burden and ‘ought to’ end one’s life, and a general trivialisation of suicide. Family situations are often complex and murky when viewed from the outside and it is easy to imagine that in any assisted suicide determining the extent to which living relatives encouraged or pushed their late relative into committing suicide is difficult in the best of circumstances.

In addition, suicidality often comes hand in hand with severe depression, and can be nothing more than a passing phase. It is likely that a large minority or even a majority of readers will experience depression at least once in their life, and if dealt with sensitively and appropriately it may be that any related death wish goes away in as little as a few months.

This is the reality on the ground for family doctors, the police, social workers, nurses, psychiatrists, palliative medicine doctors and other health workers. Any discussion of assisted suicide and euthanasia is inseparable from this reality; it is weak merely to argue ‘Yes, but if you are of sound mind you should be able to choose to end your own life’, which ignores the broader social context that all deaths happen in. However, ultimately autonomy and the freedom to choose one’s own care is a fundamental principle of liberty and of medical ethics and it is the ideal that we must strive towards.

Those countries where euthanasia or assisted suicide is legal usually have a number of safeguards present, such as requiring the approval of two doctors and/or a panel of experts, or as in Switzerland police inquiries after the fact. In the EU, euthanasia is legal in the whole of Benelux (fun fact – legalisation caused a minor constitutional crisis in Luxembourg when the Grand Duke refused to sign the law). However, in Netherlands, which has administered drugs for euthanasia in 1,000s of cases, the United Nations Human Rights Committee has highlighted concerns that regulation may be too lax.

In summary, in countries where assisted suicide is legal, a fairly large regulatory apparatus is necessary but perhaps not sufficient to prevent abuses. It also seems that there is some correlation between stringency of regulation and number of reported cases.

And what about doctors’ role in all this? Well, repeated votes at the BMA suggest that most doctors (or at least their professional representatives) don’t want to touch assisted suicide with a bargepole. Interestingly however, the Royal College of Nurses recently voted for a ‘neutral’ position. In practice if assisted suicide is decriminalised in the next few months in the UK,  nurses and doctors might be able to assist in some way pending review by regulatory bodies such as the General Medical Council.

So even if assisted suicide is decriminalised, it will continue to be a messy and controversial business. Find out more in my next ethics posts as the story unfolds.

Jul 06
Posted by: nicholasswetenham  

 

A lab mouse

Animals are an invaluable resource in all areas of biology and biology-related research, and cannot be replaced by ‘alternatives’ as advocated by many animal rights activists and many Green Parties across Europe. In this series of posts, I will explain several interconnected reasons for experimenting on animals drawing examples both  from everyday life and hard science. I will also explore the ethical dimensions of using animals and consider whether the legal framework we have in place is fit for purpose.

Drug discovery is the easiest to understand: in order to discover and develop safe drugs that can save human lives, we experiment on animals. The Green Party of England and Wales disagree. Here is an excerpt from their Animal Protection policy:

Experiments on animals are unreliable as a guide to human biology. Different species react differently to drugs and toxic substances. Many drugs that cause damaging side-effects in people have passed animal tests. There are viable alternatives to animal testing including epidemiology, the use of cell cultures, human tissue and computer simulation. The Green Party would redirect research funding to such alternatives.

These are commonly repeated beliefs from animal rights campaigners. For example, People for the Ethical Treatment of Animals (PETA), a high-profile group, campaigns against animal testing as one of its core issues. You can see a collection of documents listing their beliefs here.

A counterweight to this group is the Oxford-based pro-animal experimentation group Pro-Test.

So are animal tests necessary for drug discovery and development? I’m going to briefly outline the process of drug discovery and we’ll see whether it’s truly possible. The steps involved in modern rational drug design (the old fashioned way basically just trial, error and luck) are: 1. Drug target identification  2. High-throughput screening for candidate drugs and refinement 3. Preliminary testing of candidate drugs on cells or animals 4. Clinical trials in humans

1. Drug target identification

We now understand how various biochemical ‘pathways’ (chains of interacting components) operate in cells. When we fınd a pathway involved in disease, we hope that by changing its activity we can slow down or stop the disease process. This means that generally, we are aiming for something when we test drugs and not randomly subjecting animals to experiments.

2. High-throughput screening

To find potential drugs, libraries or collections of ‘drug-like’ molecules are tested for their binding to the target. Anything that binds to a biological molecule might modify its activity and be a potential drugs. Many hundreds of potential candidates emerge.

3. Preliminary testing

This is the contentious part. The drug is tested for its potential. Sometimes we use cells, but often we use ‘animal models’. These are animals that are bred or engineered to have a similar disease process to humans. This allows us to test the potential safety and efficacy of drugs. Although in a few unfortunate cases this method will not pick up dangerous drugs, it usually does.

4. Clinical trials

The drug is tested on humans in several phases of increasingly larger groups starting with just a handful.

What about Computer models?

Mark Chu-Carroll at Good Math, Bad Math made an excellent post answering advocates of computer models:

a simulation can only do what you tell it to. If you don’t already know how something works, you can’t simulate it. If you think you know how something works but you made a tiny, miniscule error, then the simulation can diverge dramatically from reality.

And epidemiology?

Epidemiology is part of the great tradition of experimental medicine and can help identify causative factors of a disease, but it can’ t test a drug’s safety.

Conclusion

Testing drugs on animal is unpleasant. No one likes doing it. Do not be fooled into thinking scientists are using animals unnecessarily for perverse reasons. There is only one alternative to testing drugs on animals: testing them on humans. It is your decision which you value more. That said however, we can all agree that where possible we should reduce usage of animals for experimentation, and that research into ways of doing this should be well funded.

I urge you to read as much as you can on this subject, think for yourselves, and arrive at a rational, evidence-based conclusion. Question everything.

- Nicholas Swetenham