Synthetic Biology: With great knowledge comes great responsibility

[This article was first written as an editorial for  the June 2019 issue of The Biochemist, magazine of The Biochemical Society. The issue focused on Synthetic Biology and appeared shortly after the death of recombinant DNA pioneer Sydney Brenner.]
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Since the publication of our previous issue of The Biochemist, we have been saddened to hear of the death of Sydney Brenner (see this link for a fuller obituary). Brenner was a giant of molecular biology in the second half of the 20th Century, conducting pivotal experiments and generating insights on many aspects of biochemistry which have become the cornerstone of our understanding of how life works. These include the existence of the triplet codon for ‘reading’ nucleic acids to make proteins, the existence of messenger RNA and, prior to that, fundamental work on the structure of bacteriophage. Brenner was a pioneer in establishing the nematode worm Caenorhabditis elegans as a model organism, a decision that was to lead to his sharing the Nobel Prize in Physiology or Medicine in 2002 for “discoveries concerning genetic regulation of organ development and programmed cell death”.

In the context of the current issue, which has a focus on synthetic biology, it is also relevant that Brenner was a key participant at the famous February 1975 conference at Asilomar, California. The meeting had been organized to discuss the safety and regulation of the emerging field of recombinant DNA technology. Over 100 leading molecular biologists were present, and the consultation was conducted in the presence of sixteen members of the press. Journalists included Michael Rogers from Rolling Stone who described Brenner as “the single most forceful presence at Asilomar” (Fredrickson, 1991). Amongst Brenner’s major contributions was promotion of the concept of ‘biological containment’ alongside physical interventions to safeguard against the accidental spread of genetically modified organisms.

The technology debated at Asilomar, combined with forty years of subsequent innovation are, of course, pivotal to synthetic biology. Concerns about ‘bioerror’ as well as bioterror persist, especially when some of the intended applications (e.g. bioremediation) would require the release of altered organisms into the environment. Much of the focus of this field remains the remodelling of microbes to carry out specified function, an emphasis which is reflected in several articles in this issue. As will also be evident, however, developments are occurring in a variety of other organisms. These include altering plants to be biofactories to manufacture a chosen product, or exploiting our knowledge of molecular biology to reduce unwanted effects of protein therapeutics whilst retaining the desirable characteristics.

The potential applications of synthetic biology are extraordinary, and we are certainly only at the beginning of this revolution. We need, however, to heed the spirit of Asilomar and proceed with due caution, in case our knowledge outstrips our wisdom.

Fredrickson D.S. (1991) Asilomar and Recombinant DNA: The End of the Beginning, in Biomedical Politics (ed: K.E. Hanna). Washington DC, USA: National Academy Press

A copy of the original version of the article can be found here.

What is neuroethics?

[The following text was originally written as an editorial for the October 2018 issue of The Biochemist, magazine of the Biochemical Society. The full issue can be found here].

For many readers of The Biochemist, it will have been curiosity about the inner workings of the body, and what goes wrong in states of disease, that triggered their journey into studying molecular biology. No organ of the body is more important than the epicentre of that very curiosity, the brain. Through a variety of approaches, we are building understanding of the functioning of both the healthy and the diseased brain.

These discoveries raise a plethora of ethical questions, and represent one dimension in the burgeoning field of Neuroethics. As far back as 2002, philosopher Adina Roskies noted that Neuroethics encompassed both the ethics of neuroscience and the neuroscience of ethics. Even sticking, in the present context, to ethical issues associated with biochemistry, there are plenty of examples where dilemmas are raised.

  • If someone’s aggression is linked to possessing the “wrong” Monoamine A oxidase gene and, in consequence, they are less efficient at breaking down neurotransmitters, can they be held less culpable for criminal behaviour than someone with the more “restrained” allele?
  • As we start to understand more about the molecular changes (e.g. epigenetics) underlying the influence of environmental factors on behaviour, can it be acceptable to artificially mimic those changes in order to achieve the same (or a different) outcome?
  • Is there an ethical difference between providing Ritalin to a boy with attention deficit, in order to move their concentration more into the “normal” range, and offering the same drug to a university student hoping to avoid distraction in the run-up to an exam?
  • Is it morally acceptable to conduct brain-based research on model organisms, when the relevance of that research become more applicable to human health as the animal studied get closer in mental capacity to humans?
  • If, as an alternative, we use human brain tissue organoids in research, is there a point in their development when they are “too human” to use in this way? And would transplanting human brain organoids into rodent models be an acceptable alternative to research on primates?

A PDF of the article can be found here.

Forty years of IVF

I mentioned in a recent blog post (here) that I was intending to re-post some of the Editorials I have written for The Biochemist over the previous two years. Here is the first, from June 2018, in which I reflected on forty years of IVF in the introduction to an issue on Fertility.
The Editorial can be found here.
The full issue on Fertility can be found here.
And the text is also reproduced below
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One of the unsettling aspects of growing older is the realization that events which occurred within your own lifetime are considered by others to be history. This experience struck me for the first time when one of my children was studying the fall of the Berlin Wall for their GCSE course.

2018 marks the 40th birthday of Louise Brown, the first baby produced by IVF (in vitro fertilization). For many readers of The Biochemist this pre-dates their own birth, and definitely falls into the category of history. In 1978, I was a schoolboy who hadn’t quite qualified for long trousers. I was sufficiently news-savvy to appreciate that a significant breakthrough had occurred but without being clear on the details. (In truth, I rather suspect this caveat could also have been applied to my understanding of the more traditional route to conception). In the intervening period, IVF has become the cornerstone of a broader array of assisted reproductive technologies (ART), some of which are discussed in more detail in articles in this issue.  Continue reading

Questions at the Edge of Consciousness: A review of “Into the Grey Zone”

Imagine (and I hope this is a theoretical scenario rather than a real experience) that a friend is involved in a road traffic accident. The collision leaves them in what neuroscientist Adrian Owen terms the “grey zone”; the patient is alive (and does not require artificial ventilation) but they are in a “vegetative” state. Their body has periods when they appear to be awake, but they do not demonstrate any awareness of their circumstances. In the absence of intentional movement, how can we be sure that they are not, in fact, conscious – hearing the conversations next to their hospital bed, maybe even experiencing pain?

ITGZFor a long while this question seemed unanswerable. However a flurry of scientific papers, published about a decade ago, demonstrated beyond reasonable doubt that it was possible to communicate with some patients in an apparently vegetative state. Now Professor Owen has published a memoir Into the Grey Zone capturing his experience at the heart of that groundbreaking work. (I couldn’t wait for publication of the Anglicised version, so I actually have “…Gray Zone“, but am assured that aside from spellings and the occasional idiom, the contents are the same. I notice on social media that Owen himself refers to the book at ITGZ which not only saves a few characters but neatly side-steps the issue of the different title.)

Whatever we choose to call it, this is a remarkable and moving read – I cannot think of any other book that has simultaneously thrilled me with the clear and logical presentation of scientific experiments and moved me to tears with their implications of the experiments for patients and their families. What follows is my rather lengthy summary of the book, followed by some specific reflections. If you want to skip directly to the latter, click here.

The book follows a general pattern in which each chapter introduces us both to the individuals who had slipped into the grey zone, and to the emerging tools of neuroinvestigation which enabled Owen to demonstrate that many of these patients, perhaps 15 to 20% of those previously considered as “vegetative”, do in fact retain some level of consciousness.

The first chapter The Ghost That Haunts Me is slightly different. It features two central characters who slip into the grey zone, but neither is a patient of Owen. Instead they are his mother, who developed a brain tumour, and his former lover Maureen who suffered a subarachnoid haemorrhage that left her in a vegetative state. Continue reading

“Are you my mummy?”*: Diverse notions of “motherhood” in the IVF era

Back in autumn 2017, I was asked to be a contributor at the Edinburgh Biomedical Ethics Film Festival on the Ethics of Surrogacy. As part of the weekend we watched the 2016 documentary Future Baby, and the 1990 film version of The Handmaid’s Tale.

It was during my preparation for that event that I found myself ruminating on the diverse tasks that constitute being a mother. The anniversary of IVF brings this back into my thoughts.

There are, in essence, three contributions that a mother would naturally make:

  • producing the egg which provides half of the chromosomes for the resulting child (plus nutrients and some other genetic material via the mitochondria),
  • offering the womb in which the baby will develop (whilst receiving both nutrition and epigenetic influence on gene expression), and
  • caring for the infant after birth, and as they grow on to eventually attain their own independence.
motherhood too

Motherhood can now be subdivided into different roles (cartoon inspired by Morparia original)

These phases could be summarised as the genetic, the gestational and the nurturing dimensions of motherhood (the term “social” is sometimes used in the literature to cover this third category, but I prefer to the notion of nurture). Continue reading

Can “Synths” and “Posthumans” have Human Rights?

In the recently-finished third season of the intelligent drama Humans [spoiler alert…], the government has set up a Commission under the chairmanship of Lord Dryden to consider the legal status of synthetic robots (Synths). These creatures had become conscious at the end of the previous series (if you want to know more, I do recommend that you watch the box set).

chan

Mia (Gemma Chan) is a central character in the first three seasons of Humans

Against that backdrop, I was especially interested to read a new paper in the Medical Law Review by David Lawrence and Margaret Brazier. Legally Human? ‘Novel Beings’ and English Law considers ways in which the European Convention on Human Rights and English case law might be brought to bear on the legal status of human-like creatures. The authors favour the description of such beings as “sapient” rather than the more common “sentient”, not least as sentience was famously used by philosopher Jeremy Bentham as justification for broadening protection from suffering to non-human animals.

legallyhuman

Lawrence and Brazier examine three types of entity whose production is scientifically-plausible using existing technologies (whilst acknowledging that other methods might emerge in the future). These creatures are: Continue reading

Avoiding Scientific Misconduct in Prague

I recently spent an excellent few days in Prague, attending the 43rd FEBS Congress, at which I gave a talk about the importance of bioethics teaching, and ran a workshop on developing case studies in ethics teaching. A session on the final morning Scientific (mis)conduct: how to detect (and avoid) bad science illustrated one reason why this is a crucial dimension in the education of scientists.

prague1

I live-tweeted the presentations and organised them at the time within five threads. The post below represents a first attempt to use Thread Reader (@threadreaderapp) which operates a very straightforward “unroll” tool. Following the sad demise of Storify, I was curious to see if this would be a suitable alternative for curation of tweeted content. I have elected to offer both links to the unrolled threads and screenshots of the resulting notes. I’m relatively pleased with the outcome.

Getting back to the content of the session, it proved a really insightful overview of several aspects of research misconduct, and publication ethics. Continue reading

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