Synthetic biology: “Playing God”?

December 31, 2012
playing god

My notes on the episode, divided into principal sections

On reflection, I think 2012 was a good year for the BBC’s flagship science programme Horizon. One of my favourite episodes came way back in January, when Dr Adam Rutherford fronted the one hour documentary Playing God on the emerging discipline of synthetic biology. From a bioethical standpoint, this was a particularly strong episode with good coverage of the science, the potential advantages and the potential pitfalls of synthetic biology clearly demonstrated. My notes on the episode are available here.

The full episode is no longer on iPlayer, but a series of clips are still on the official Horizon website and are mirrored on the BBC’s official YouTube channel (in the list below the title link goes to the BBC Horizon site, the end link to YouTube). In terms of potential clips for teaching it therefore makes sense to start with these sections although, as we will note below, the best section on ethics is not included among the official clips.

    • Title sequence (duration 1:47) Content: The opening sequence sets out the key themes for the programme – the contrast of billions of years of evolution versus the emerging potential to predetermine the development of new species; life as a programmable biological machine. This power has great potential for good but might be abused. Comments: Of the five available clips, I don’t think this would be my first choice for introducing the issues as there isn’t quite enough detail without subsequently seeing those themes expanded in the rest of the programme. (YouTube).
    • An animal that shouldn’t really exist (duration 3:14) Content: Rutherford visits a farm in Logan County, a research facility belonging to Utah State University. Prof Randy Lewis explains the attractive properties of spiders’ silk to him, and the fact that the spiders’ cannibalistic tendencies make them impossible to farm directly in order to produce adequate quantities of the material. The solution? Transferring the gene for the silk protein into another animal to produce an organism “part spider, part something else”, with the next clip revealing that to be a goat.  Comments: This clip and the next are actually from the same section of the programme and could usefully be shown back to back (total = 6 mins). (YouTube).
    • The goats with spider genes and silk in their milk (duration 2:43) Content: Continuing their discussion at the research farm in Utah, Rutherford is introduced to the “spider goats” by researcher Randy Lewis. The goats have been engineered to produce the protein for spider silk and extrude it in their milk. When challenged that this is “bizarre”, Lewis counters that he considers the goats to be  “absolutely normal”. The clip goes on to show the goats being milked but does not include extraction of the silk, which was shown elsewhere in the programme Comments: I don’t like the use of the term “spider goat” as it implies something much more of a hybrid or a chimera than the reality – which is a goat with one gene added. We have discussed some of the issues surrounding such transgenic animals in other posts on BioethicsBytes, especially in regard to the Animal Farm documentary series and associated extended commentaries. Nevertheless, this section does usefully highlight some of the attractive features of this kind of bioengineering – the capacity to produce a valuable protein in an easily harvestable form (YouTube).
    • Playing God, by recreating life (duration 4:38) Content: This section discusses the 2010 announcement of the production of Synthia by Craig Venter and colleagues. Synthia, or Mycoplasma mycoides JCVI-syn1.0 the more formal name for the organism, is “the only lifeform on earth whose parent is a computer”. (this is a reference to the fact that the sequence of DNA in Synthia was decided in advance using online genome databases and then the DNA molecules themselves were produced chemically as a series of shorter sections assembled together to make the complete genome for the cell). The clip includes a section where Rutherford uses white and red candle wax to draw out cells of two different species (more of that in a moment). As he points out Venter’s team can’t truly be said to have “created” life since – aside from addition of a few DNA ‘watermarks’ to identify the species – the DNA code had essentially been purloined from another related bacterium. “Recreated” or “rebooted” might be nearer the mark, Rutherford suggests. Even putting the hype to one side, he emphasises that this is an unprecedented degree of control over a living thing. Comments: Overall this is a nice section, summarising the achievements of making Synthia, without getting too sucked in to the hype. On the downside, the demonstrations are a little confusing – the drawing of cells using candle wax inadvertently implies that the cells have a nucleus which, as bacteria, they don’t (YouTube). 
    • Mind control (duration 2:22) Content: Rutherford visits Ed Boyden in his lab at the Massachusetts Institute of Technology to discuss his pioneering work in synthetic neurobiology, a step from controlling microbes to controlling the brain, the  “most precious part of our anatomy”. Comments: A slightly frustrating clip, it ends just as it’s getting to the interesting bit! (YouTube). 

Frustratingly, the producers have not made available the clips with the most overt bioethical content. If you have access to the full programme (TRILT code: 0243AA4F; available as an off-air recording to BUFVC members) then I would favour the following sections:

  • 16:16 to 20:55 where the “biobricks” approach is raised
  • 25:56 to 33:11 manufacture of “biodiesel”
  • 41:21 to 45:33 introduction to garage or DIY biology, aka “biohacking”

Ethical concerns include:
– safety and the risk of modified organisms escaping (though this is partly countered by reference to the inclusion of inbuilt metabolic “kill switches”, see section 34:18 to 36:02). This is a consequentialist argument.
– exploitation of the poor, with necessary agricultural land being given over instead to growing plants as feedstuff for the bioplastics industry (section 36:03 to 38:02). Again a consequentialist argument.
– risks of bioterrorism, especially as the necessary molecular biology moves out from the lab and into suburban garages (section 38:03 to 41:20).
– playing god, a deontological argument, raised in the clip of the same name.

Rutherford’s closing statement nicely encapsulates the situation we are in at the moment “Whatever you think of the uneasy bargain that surrounds synthetic biology, one thing is absolutely clear. We have created for ourselves unprecedented power over life itself” (58:22).


Brain and Awareness – The Secret You (Horizon)

November 7, 2009

Mathematician Marcus du Sautoy is becoming an increasingly regular front-man for the BBC science documentary Horizon and, to date, his contributions have always been satisfyingly informative. The recent episode The Secret You is no exception.

In his quest to discover the underlying biochemistry and physiology of consciousness, du Sautoy visits a number of laboratories around the world where self-awareness and the notion of “the inner me” are being investigated. In doing so, he frequently participates in experiments; at one point he quips “another day, another scanner”(50:49).

scanner

Marcus du Sautoy takes part in many experiments as part of his search for the basis of consciousness

There are a raft of ethical questions which arise from functional Magnetic Resonance Imaging (fMRI) and other neuroimaging methods, some of which I have written about elsewhere (see Disorders of consciousness: do state-of-the-art neuroimaging techniques shed new light on the brain-injured patient?).

For me, the most interesting ethical questions in the programme arise from the work of Professor Adrian Owen. du Sautoy and Owen discuss experiments conducted with patients in PVS, a Persistent Vegetative State (16:44 to 19:22, though the discussion makes most sense if you start at 15:30).

owen4

Prof Adrian Owen of Cambridge University has made exciting discoveries about the awareness of a patient in PVS

Previously our abililty to tell whether or not a PVS patient was genuinely conscious was constrained by the fact that they had no physical ability to demonstrate their awareness. In ground-breaking experiments, however, Owen and his colleagues have communicated with patients by asking them to imagine performing certain tasks, for example playing tennis, and using fMRI to show that the appropriate areas of their brains are activate. By developing this further, it is possible to get the patient to imagine two different activities which are clearly distinguishable from one another in terms of brain activity. These can then serve as proxy signals as “yes” and “no” answers to questions posed.

owen1

A patient could be trained to make certain areas of her brain active as a proxy answer to questions posed by researchers (e.g. by imaging she was playing tennis or walking around her house)

These experiments have revolutionised our understanding of brain-injured patients. In particular it brings into question the practice of withdrawing food and water from patients in PVS on the assumption that the are not aware.

Horizon: The Secret You (TRILT code 01210858) was first broadcast on BBC2 on 20th October 2009.


Horizon: Jimmy’s GM Food Fight

December 8, 2008

In recent months, the debate that surrounds Genetically Modified (GM) food crops has been reignited by attempts around the world to deal with food poverty in developing countries and the ever increasing price of food across the globe (See The GM Food Debate). Concerns about both the availability and price of food has meant that people are now looking to viable agricultural alternatives to increase food production, including the potential contribution of GM technology. Jimmy Doherty (also seen on Jimmy Doherty’s Farming Heroes and Jimmy’s Farm) is a strong advocate for traditional and sustainable farming but, as he explains (Start – 00:02:00):

Jimmy Doherty "I love the way that I farm, but I am, I am a realist and I realise that the way that I produce food will not feed the world. A lot of people think that the only way to do that is to use biotechnology, GM crops and I'm not sure about that. I don't know if it is safe or not? I don't know what the consequences are? But what if the answer to feeding the hungry is using biotechnology?"

Jimmy Doherty "I love the way that I farm, but I am, I am a realist and I realise that the way that I produce food will not feed the world. A lot of people think that the only way to do that is to use biotechnology, GM crops and I'm not sure about that. I don't know if it is safe or not? I don't know what the consequences are? But what if the answer to feeding the hungry is using biotechnology?"

Horizon: Jimmy’s GM Food Fight is a BBC 2 programme first broadcast on 25th November 2008 at 9:00pm. There are also two clips from the programme available permanently online: ‘How to create a GM plant’ and ‘Amish farmers embrace GM crops’.

59pm 23rd December

BBC 2 Horizon: Jimmy's GM Food Fight. Full version available on the BBC iplayer until 08:59pm 23rd December

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Epigenetics – The ghost in your genes

June 30, 2008

 
Epigenetics – Turning genes on and off  

The BBC Horizon documentary The ghost in your genes, successfully explains a particularly complex field of science. Genetic inheritance has historically been thought of as involving the transmission of DNA from one generation to the next affected by occasional mutations in the DNA itself (00:04:37 – 00:05:50). “Up to now, inheritance is just the genes, the DNA sequence. I suspect that we’re going to be able to demonstrate that inheritance is more than that”, explains Professor Marcus Pembrey from the Institute of Child Health, UCL. A few scientists had hypothesised that the conventional genetic model and mode of inheritance was too simplistic to explain the complexity of human beings. The revelation that the human genome likely contains only about 30,000 genes (00:08:54 – 00:11:33), coupled with increasing experimental evidence, now leads scientists to believe that other factors allow genes to be switched on and off in response to environmental stimuli. The consequences of which may affect subsequent generations.

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Designer Babies – three documentaries

July 12, 2007

The term ‘designer babies’ is one frequently used in the media, though scientists find it ‘slippery’; geneticist Steve Jones says “the phrase ‘designer babies’ just fills me with despair; it promises so much, but delivers nothing”.  Instead, scientists such as Jones would generally prefer to consider individually the variety of technologies that are embraced by the term, notably pre-implantation genetic diagnosis (PGD), gene therapy and genetic enhancement.  Other entries on the BioethicsBytes site have reviewed resources about these developments (see, for example, the post on the A Child Against All Odds series and Bioethics Bytes Guide to Streamed Media for discussion of PGD, and Horizon: Trial and Error on gene therapy).

 

Having said that, this entry is headed Designer Babies because the phrase has been used directly in the title of a number of documentaries, including the three programmes discussed here.  These are: Life and Death in the 21st Century: Designer Babies (Horizon); Who’s Afraid of Designer Babies? (also Horizon); and Designer Babies (National Geographic). Each episode will be considered in turn, and some comparisons and recommendations are drawn together at the end.

 

Life and Death in the 21st Century: Designer Babies
The BBC Horizon series marked the millennium with a series of three programmes examining the potential impact of science on human life in the near future.  The final episode, Designer Babies (6th January 2000; TRILT identifier: TVI16522) had actually been broadcast previously under the title Babies of the millennium: designer babies (7th April 1999; TRILT identifier: TVI4440). A transcript of the programme can be found on the BBC website.

 

We will only discuss this episode briefly, since the 2005 Horizon Whose Afraid of Designer Babies? is, to a large extent, an updated version.  This programme considers many ethical issues, focused around two core questions: Can scientists create designer babies and, if they can, should they do so?  The episode opens with a number of prominent scientists and ethicists giving their views, and this could serve as a handy scene-setter for a classroom discussion.  Indeed, the main value of this particular programme is the barrage of quotable quotes (the transcript, linked above, is very helpful in this regard). Not least Princeton Geneticist Lee Silver’s closing comment “In a society based on market principles I don’t think there’s any way to stop the use of this technlogy by those who  have money”.

 

Initially, the episode focusses on the Abshire family.  Maigon Abshire, the first daughter of Renee and David Abshire, died aged three from TaySachs, a disease of the central nervous system.  Desperate to avoid their next child having the same fate, the Abshires were the first in the USA to use pre-implantation genetic diagnosis (PGD).

 

Later, there is discussion about the production of Dolly the Sheep, and more particularly Polly, who was the first evidence that the cloning process can be tweaked to include the addition of new genetic information into an embryo and, hence, into all the cells of the resultant organism. In the case of Polly, the human gene for Factor 9, a protein involved in blood clotting, was introduced into an egg at the start of the cloning process.  The resultant sheep produced large amounts of Factor 9 in her milk.

 

Finally, there is discussion of how much of our adult form, both our physique and our character, is down to our genes (a rehearsal of the nature v nurture debate), and consideration of the expense of the processes, with the concern that the benefits of the technology will only be available to the rich.

 

Who’s afraid of Designer Babies?

In many ways, Who’s Afraid of Designer Babies? (48 minutes; 24th February 2005; TRILT identifier: 00513446) is a conscious updating of the earlier Horizon episode and manages to bring both the science and the ethics into rather sharper focus.  The programme helpfully disentangles the various technologies that are often lumped together in discussions about designer babies and deals in turn with PGD, gene therapy and cloning.  Depending upon available time, this three-section structure may make the episode particularly useful for teaching; each section might form the basis of three linked lessons.  Both a summary of the programme and a full transcript are available from the BBC website.

 

Who’s Afraid… begins with consideration of PGD.  We are introduced to Philippa Handyside who carries a chromosomal abnormality and turns to PGD following several attempts to establish a pregnancy by natural means.  In this section we are not only presented with a clear explanation of the PGD technique (00:05:00 – 00:08:45) but also a demonstration of the emotional and physical cost of the procedure (00:14:11 – 00:18:36). Philippa describes the fertility treatment needed for PGD as “horrendous…just absolutely horrific” (00:15:27) and the devastation she felt when told the treatment had not resulted in an error-free embryo. After further rounds of fertility drugs she eventually gave birth to a healthy son. 

 

This, of course is controversial enough in its own right, embryos that are not selected do not get implanted and do not get the opportunity to develop into a child.  The programme hints at future controversies in this area. Using a quote from Princeton geneticist Lee Silver (00:12:40) and an old clip from another BBC science series Tomorrow’s World, we are presented with a brief discussion of the potential to move from screening for particular diseases to the potential to select between different embryos on the basis of anticipated intelligence or musical ability.  There are two limitations here.  The first is technological – you can only screen any one cell at any one time for one or two genes, not a whole battery of tests. Secondly, and most importantly, the characteristics can only be chosen from amongst the alleles carried by the parents, if a trait is not represented in their genomes it is not available. As Joyce Harper from University College London puts it “We’re not designing any babies.  We’re not doing any genetic manipulation of the embryo.  We can only select the embryo that the couples produce.  So, if they’re not going to produce an embryo that’s very intelligent, we can’t select for it” (00:22:00).

 

It is at this point (00:22:35) that the episode moves on to think about gene therapy as a means to actually altering an individual’s genetic profile.  The ground here has been covered previously in the Horizon episode Trial and Error (in fact some of the footage is exactly the same).  The focus is on the work of Dr French Anderson, including his 1990 success in using gene therapy to treat Ashanti De Silva who had been suffering with a severe immune system deficiency caused by a genetic mutation. The episode also touches on the devastating blow the field received in 1999 when teenager Jesse Gelsinger died during a gene therapy trial in Pennsylvania.  The section from 00:27:00 to 00:33:48 raises the ethical questions most clearly; in particular, the risks of an introduced gene getting into the germ line cells and being passed on to subsequent generations.
 
In the final section of the programme, the focus shift to cloning technologies.  As with the earlier Life and Death…, both the cloning of Dolly the Sheep (00:34:56 – 00:35:38) and the subsequent production of Polly (00:35:40 – 00:37:30) are discussed.  Polly, you will recall,  is a genuine designer offspring; she has been genetically modified by the insertion of the human gene for blood-clotting protein Factor 9 into her genome.

 

Despite this apparent success of cloning mammals, a number of practical limitations and ethical qualms are identified.  Cloning remains an imprecise science with substantial attempts leading to abnormality and loss of life.  Added to this, even the viable products of some experiments have turned out to be rather different from the expected outcome; the programme illustrates this with reference to a genetically modified ‘supermouse’ with big muscles but an unexpectedly placid personality. 

 

The programme concludes with a visit to the Life Centre in Newcastle, to discuss the relevance of their work on “therapeutic cloning”.  The emphasis, in fact, is that work on manipulating embryonic stem cells, which is the basis of therapeutic cloning, is only looking for ways to treat diseases (though the impression given that no-one here is interested in adapting this work to make designer babies demonstrates a wilful avoidance of the fact that mavericks elsewhere may be very keen to exploit the lessons learnt through their research).  This section certainly contains a nice synopsis of the goals of therapeutic cloning (00:41:35 – 00:45:48). 

 

Overall, the programme gives helpful insights into a range of current developments in biomedicine whilst emphasising that ‘designing’ babies remains some way off.

 

National Geographic: Designer Babies

Designer Babies, from the National Geographic channel (60 minutes, TRILT identifier: 00564089), echoes many of the ethical and practical points raised in the two Horizon documentaries.  However, it has an extended section on PGD and therefore may be the particularly useful if you are looking for a detailed consideration of this topic. 

 

An Australian boy with Hyper IGM syndrome, an X-linked genetic disease, is the focus for much of the episode.  His family seek to use PGD to produce another child selected to be both free of Hyper IGM and also a tissue-match for the older boy so that stem cells harvested from the umbilical cord can be used to treat the older sibling (there are echoes here of UK case involving the Hashmi and the Whitaker families).  The story unfolds to show how the parent overcome the emotional and financial cost to have a new child who will provide the life saving stem cells their first son needs.

 

Unlike the Horizon documentaries, the issue here is one of “saviour siblings”, the production of a “spare parts baby” (00:02:30) and this raises additional ethical questions. For example, the family are concerned about the emotional burden on the new child when it grows up knowing that they were conceived to save their sibling. How would the child feel if, despite all of these efforts, the treatment fails? These are just some of questions raised in the programme.  On the one hand you have parents desperate to do everything they can for their child “Until you’ve got a child, who is in a certain situation, I don’t think you can predict what decision you will make” (Mother; 00:01:31) and on the other you have people worried about the consequences for the new born “We need to do research into how our children are going to be affected by this” (Ethicist Dr Jeffrey Nisker; 00:12:55).

 

The programme also picks up on the use of PGD to select the gender of a child for non-medical reasons, e.g. a mother of four sons desperate to have a girl, and examines some of the ethical issues raised by this application of the technology. (Again, there are echoes here of UK cases, such as the Mastertons and the Chenerys). 

 

In light of these worries, the programme examines the strengths and weaknesses of regulation and ethics committees regarding the uses of PGD. Views expressed range from Nisker, who fears that “in ten years the commercial companies that have been distributing this agenda will have altered us as human beings” (00:25:38) to one mother who states that she “didn’t know why she had to sit in front of an ethics committee to explain why she wanted a child” (00:27:10).  Dr Greg Stock, a bioethicist and prominent commentator in this arena, agrees.  He believes that the best people to make such a decision are the parents and the individual, since they are the ones directly affected. Some children, it is reported, have died while waiting for a decision by the regulatory authorities.

 

This debate moves on to a discussion regarding who has the right to decide who should, and who should not, have children.  Lessons from the Nazi use of eugenics (00:33:49) are used to reinforce the view that central government is not the best place for such decisions to be made. What about parents’ rights to deliberately select a child that is deaf, and thus in the eyes of many people, “disabled”?  The particular focus is on a couple that have both been deaf since birth but naturally conceived a hearing child.  They see deafness, not as a disability, but as a part of their identity (00:36:02).

 

Designer Babies is an excellent resource to raise some of the ethical issues being raised by the more recent advances in PGD. It also features descriptions of what is involved in PGD (00:04:02 – 00:06:02), the history of PGD (00:07:07 – 00:08:40) and the genetic screening that takes place in PGD (00:20:27 and 00:40:00).

 

Which episode is the ‘best’ for teaching? 
All three documentaries contain short sections that would prove very useful for raising discussion on the science and/or ethics involved in ‘designer babies’.  Life and Death in the 21st Century certainly does not cover a number of significant developments which have occurred since it was made.  If you have a copy languishing on the video shelf, it is certainly worth a watch; many of the ethical arguments are still valid.  If, however, you’ve got access to Whose Afraid of Designer Babies? or National Geographic Designer Babies these are probably better.  Either would be highly suitable for showing to a class; the preference may boil down to availability.  At the time of writing (July 2007), the National Geographic programme has not been repeated in the UK since early 2006, whereas Whose Afraid… has been showing regularly on UK Documentary. For this reason, we plan to use the latter as the focus of some additional teaching resources – details to follow.

 

David Willis and Chris Willmott


Face transplant – Horizon

December 7, 2006

The World’s First Face Transplant is an episode of the BBC science documentary series Horizon.  It focuses on the circumstances surrounding the transplant of the lower part of a face for Isabelle Dinoire after she was mauled by her dog.

In terms of discussion starters, the best material available at the moment is actually on the BBC website for the episode.  A series of short interviews with surgeons (Nick Parkhouse – anti, Peter Butler – pro) and facially-disfigured individuals (James Partridge – anti, Simon Weston – pro, Sundeep Hunjan – pro) nicely set out some of the principle arguments for and against face transplantation. 

Perhaps unsurprisingly, the programme itself contains several sequences of surgery being performed and also has images of Isabelle in the period between the attack and before the operation.  In consequence, it may be inappropriate to show the whole episode to some groups of students. 

A section starting at 35:02 and running to 35:43 has a montage of newspaper headlines and TV news reports about the operation.  This helpfully finishes with the BBC anchorman George Alagiah stating that this “… raised ethical questions”.  This could be used as an intro to start discussion about what those issues might be.  Other clips offer potential answers.  In particular, some or all of a section running from 23:40 to 29:00 includes Nick Parkhouse talking about the lifelong commitment to immunosuppressive drugs and the side effects such as raised cancer risk and life shortening.  This is followed by Simon Weston saying it might not be his choice, but people ought to be given the right to have a transplant if they want.  Mention is also made of the psychological issues – of coping with a life of disfigurement v coping with looking in the mirror and seeing someone ‘not you’ looking back. 

The need for a donor to match the recipient in terms of age, gender, skin colour, blood group and the requirement to obtain permission from the donor’s family are all brought up at different points in the programme, but not in one user-friendly clip.  Comparison is made to the experience of Clint Hallam, who in 1998 was the first recipient of a hand transplant but struggled to follow the necessary regime of immunosuppressant drugs and eventually had the hand removed.

This episode was first transmitted 17th October 2006 (TRILT code: 005CBF55)


Gene therapy – Horizon “Trial and Error”

October 18, 2006

The excitement about gene therapy received a serious blow in September 1999 with the death of Jesse Gelsinger.  At the time 18 year old Jesse was a participant in a clinical trial for gene therapy to overcome a genetic condition Ornithine Transcarbamylase (OTC) deficiency.  This documentary “Trial and Error” from the BBC’s flagship Horizon series tells the story of that trial and what went wrong.  Although the tone is sometimes unduly sensationalist, it is an excellent introduction to gene therapy.  The story is complicated by serious flaws in the conduct of the clinical trial, which can also make this a good vehicle for discussing appropriate procedures in biomedical research.  

This episode is from the 2003 season of Horizon.  It is frequently repeated on digital TV, particularly the UKTV Documentary channel.  It is also available as an off-air recording from the BUFVC (TRILT identifier 001D70CE).  Watching the whole episode is time well spent.  However, a four and a half minute clip starting at 4:40 with the voiceover “A medical revolution had begun…” and continuing through interviews with French Anderson and Dusty Miller explains the principles of using viral vectors for delivering genes into cells.  A transcipt of the programme is available on the BBC website.


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