Gene therapy

June 30, 2015

Gene therapy was the subject covered in the best video produced by students in the 2014-15 cohort of Medical Biochemists at the University of Leicester.

This is an excellent example of “whiteboard animation” – you don’t get such an effective result without significant planning. The video is wrong to say treatment of X-SCID was the first successful use; the first case involved Ashanti DeSilva, who had ADA-SCID. It does not include any coverage of genome editing methods, which are the most exciting new development in this area. Nevertheless, a very useful primer on the topic.

 


Gene therapy

June 12, 2013

Wouldn’t it be great if disease caused by possession of a faulty gene could be treated at the genetic level rather than simply influencing the symptoms? Despite some initial success, the approach has proven harder to achieve in practice than was originally envisaged.

This short video on the topic was produced by second year undergraduates at the University of Leicester.

Previous Bioethicsbytes posts on the same theme please see the Categories menu to the right. Posts include:


Rise of the Planet of the Apes – a bioethical feast

December 31, 2011

Rise of the Planet of the Apes, now available on DVD, was one of the blockbuster releases in the summer of 2011. A prequel to the classic series of films (5 cinema releases between 1968 and 1973, TV spin-off and Tim Burton’s 2001 remake of the main Planet of the Apes), the new movie tries to offer a plausible mechanisms for the evolution of apes into a dominant global force.

(Warning: contains spoilers!) The new film is a veritable gold-mine for discussion of ethical topics, it would make as excellent vehicle for an engaging “film night”. In terms of bioethical issues, the film touches on all of the following:

  • Research ethics – there are lots of examples where aspects of the conduct of research are raised (some of which are picked out specifically in the list below). The motivations for doing research are touched upon at several points in the film – these include financial gain, fame and a desire to do good, both for mankind in general and specifically for the benefit of a relative in need. GenSys boss Steven Jacobs (David Oyelowo) is the embodiment of profit as a driver for research whereas Will Rodman (James Franco) represents more noble aspirations. A discussion of the ethics of research funding could follow naturally. Read the rest of this entry »

Interactive tutorials on genetics and ethics at the PHG Foundation

May 19, 2011

*** UPDATE July 2018: Unfortunately these resources are no longer available (see comment below) but I have left the post in case anyone was looking for them ***

Here’s a useful resource for teaching about bioethics and the ethical implications of new developments in genetics. The PHG Foundation website has a large number of tutorials and other educational activities on these topics. You need to register with the site to see them, but there is no fee and the “cost” of registration seems only to be a periodic e-mail newsletter also containing helpful updates.

The PHG Foundation grew out from the Public Health Genetics unit

If I understand correctly funding for the educational developments at PHG has come and gone so nothing new will be appearing in that section of their site – but the stuff that’s already there is definitely worth a look.

The tutorial on moral theories is just one of the bioethics-related resources on the PHG Foundation site


Sister (book review)

October 13, 2010

 

book cover "Sister"

Sister is Rosamund Lupton's first novel

 

(Warning: contains minor spoilers!) Not to be confused with Jodie Picoult’s My Sister’s Keeper, which is about Preimplantation Genetic Diagnosis, Rosamund Lupton’s 2010 novel called simply Sister centres on a gene therapy trial.

The Hemming family know that they harbour the gene for cystic fibrosis (CF); Beatrice – the narrator of the story – has seen her younger brother Leo die of the disease and her pregnant sister Tess has been told that her child will also be a sufferer.

At the start of the book Tess has gone missing and Beatrice flies back from the USA to look for her. As Beatrice recounts the events that follow her search for her sister, it is clear that Tess’s decision to participate in a clinical trial of a gene therapy cure for CF lies at the heart of the story.

In terms of bioethics education and an explanation of some of the ethical tensions associated with gene therapy, the stand-out passage begins on p231 when Beatrice goes to visit Chrom-Med, the company behind the official trial. Chrom-Med use of an artificial chromosome to deliver a working copy of the CFTR gene, which codes for the Cystic fibrosis transmembrane conductance regulator protein.

The passage could be read to a class to introduce some of the issues. I would suggest starting with “At just before 9.30 a.m. I arrived at the Chrom-Med building…” on p231 and running through to “When will you be testing it on humans? You’ll make a killing then, wont you?” on p233. Reading this section aloud takes about three and a half minutes.

Alternatively – the novel was adopted as the Radio 4 Book at Bedtime for ten weekday nights (24th Sept to 1st Oct 2010) and was cited in Quentin Cooper’s Material World on 27th September 2010, so there may be valuable audio extracts there. Unfortunately these shows are no longer on iPlayer but I am investigating availability of audio recordings.


DNA – The Promise & The Price

January 26, 2009
"A child born in 1953, the structure of DNA has just been discovered. 1989 and this babies genetic fingerprint can be identified. The first single gene for Huntington's disease has been discovered. 2003 this child's entire genetic code can now be read and faulty genes in his DNA can be adjusted. Another birth, but this time no ordinary miracle. The babies sex and eye colour were decided before she was conceived; also her hair, the shape of her nose and her intelligence. The date of her birth? Perhaps only a few years from now. She's born from a revolution in genetics. A revolution where each new step brings new questions of ethics and responsibility. And as the promises of the science gets greater, so do the questions for all of us get bigger."

Narrator Bill Paterson: "A child born in 1953, the structure of DNA has just been discovered. 1989 and this baby's genetic fingerprint can be identified. The first single gene for Huntington's disease has been discovered. 2003 this child's entire genetic code can now be read and faulty genes in his DNA can be adjusted. Another birth, but this time no ordinary miracle. The baby's sex and eye colour were decided before she was conceived; also her hair, the shape of her nose and her intelligence. The date of her birth? Perhaps only a few years from now. She's born from a revolution in genetics. A revolution where each new step brings new questions of ethics and responsibility. And as the promises of the science gets greater, so do the questions for all of us get bigger."

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DNA – The Promise & The Price provides an excellent resource for discussing the ethical implications of advancing genetic research, focusing on; gene therapy, stem cells and cloning. The documentary examines the frontiers of genetic science, revealing how researchers attempt to fulfil DNA’s potential to help cure and prevent disease. It also questions how some aspects of these novel technologies may have significant consequences for individuals and society. Bill Paterson: “Much is promised by genetic science, the manipulation of our genes. But can it deliver? And if it does are we ready to take responsibility for meddling with the very fabric of life itself: our DNA”.

"When it comes to medical research, any medical technology

Professor Steve Jones: "When it comes to medical research, any medical technology that works, it is very quickly accepted by the public. Ethicists may not like it, scientists may not like it, but the public, if they believe it works they will accept it, and the legislation will always follow. Ethics has always followed science, it's never led it and I don't see any reason why genetics is going to be any different. Ethicists would love to tell geneticists what to do, but I'm afraid the geneticists are not going to listen."

The topics found in DNA – The Promise & The Price include: genetics; genetic diseases; gene therapy; transplantation; stem cells; and cloning can all be found in the UK National Curriculum. Please note all timings mentioned  include advertisement breaks – (00:04:51 – 00:08:00, 00:25:31 – 00:28:40 and 00:46:50 – 00:50:00) 

Read the rest of this entry »


An epic journey – Do You Want To Live Forever?

February 12, 2008

The ethics of life extension is an immensely complex topic. It touches on a number of social and political issues, though also philosophical and metaphysical perspectives, and draws us into a consequentialist calculus over the rights of people living now and those of future, unborn generations. A number of these issues are explored in the thought provoking Channel 4 documentary Do You Want To Live Forever?, in which writer and director Christopher Sykes, follows biogerontologist Aubrey de Grey in his quest to be the man that conquers ageing.

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Biogerontologist, Aubrey de Grey (from Do You Want To Live Forever?, Channel 4, February 3rd 2007, 18.35)

In addition to extensive footage with de Grey himself, the programme also features a ‘cast of characters’, from de Grey’s mother Camilla, to award winning physicist Freeman Dyson. In interviewing each of these characters Do You Want To Live Forever? offers a number of different perspectives on the ethics of life-extension research. Although the views of different commentators are spread throughout the 75minute programme, they provide an excellent source of capsule quotes which articulate many of the ethical arguments and issues in the debate around life-extension. Read the rest of this entry »


Exploiting Genetic Knowledge – Visions of the Future (2)

January 11, 2008

The Biotech Revolution, the second episode of the BBC4 Visions of the Future series, continues to describe ways in which humanity is making a “historic transition from the age of scientific discovery to the age of scientific mastery”. Presenter Michio Kaku suggests that unlocking the basic code of life will allow us to “predetermine the destiny of life itself” and to manipulate it at the most fundamental level (Start-00:02:00).

The programme begins with Kaku having his “medical future rather than history” diagnosed via a series of genetic tests for complex diseases such as heart disease, diabetes and Alzheimer’s. He describes this as an “owner’s manual” which will enable him to have greater control of his health, and to allow others to perhaps prolong their life by decades (00:02:20-00:06:20 and 00:20:05-00:23: 20). As a scientist, he is eager to discover what secrets his genome may contain however, as a person, he says “wait a minute, this could be a Pandora’s Box… I’m looking at a side of me I have never seen before, a side that has potential medical problems lurking there”.

Some of the issues raised here mirror those found in the ITV1 broadcast The Killer in Me, which illustrated particularly well the anguish associated with having such tests and the way actions could be taken in light of the results. In this programme, in contrast, there is greater emphasis placed on the potential impact on relatives and wider society that may result from taking the tests. “We really want to respect your privacy and the privacy of your relatives” the physician emphasises to Kaku.  Much of the future of this testing, if not the present, relies upon “the last great discovery of the 21st century, the Human Genome Project”.  Kaku believes that this event holds such significance that we will look at the history of medicine in two eras, “before genome and after genome”. “Having unravelled the fundamental code of our biology the stage is set for us to manipulate it” he adds (00:06:25-00:09:20). Read the rest of this entry »


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


Gene therapy – Die Another Day

February 8, 2007

(Warning: contains plot spoilers!)  This is one of those occasions when a blockbuster film gets the science wildly wrong.  Central to the plot of the 2002 James Bond film Die Another Day is the ability of one of Bond’s foes, the North Korean Colonel Moon, to radically alter his appearance and resurface as upper crust caucasian Gustav Graves.  The change is achieved, as Bond (Pierce Brosnan) tells M (Judi Dench), by “Gene therapy – new identities courtesy of DNA transplants”. 

This is, of course, nonsense.  Although gene therapy has the potential to correct diseases resulting from a faulty copy of one gene there is never the scope to carry out such radical alterations as portrayed in this film.  Indeed, even the more limited aspiration to use gene therapy to cure relatively simple diseases has had a chequered history (see, for example, the BioethicsBytes notes on the Horizon programme Trial and Error, and news stories about leukaemia risks from one gene therapy method).

Are there any clips worth using in teaching about gene therapy?  Despite the fact that the content is way off beam, I use clips from the film as an engaging introduction to a lecture on the science and ethics of gene therapy.  The quote from Bond to M actually comes quite late in the film, long after the clinic where the work was supposedly being carried out has been destroyed.  If you have the technical capability it is worth trying to show the section 59.33 to 59.46 where M and Bond are talking (from “now tell me about this cuban clinic…” to “… didn’t know it really existed) directly before the earlier footage, 40.49 to 41.45, where Bond visits the clinic at about the same time Jinx (Halle Berry) sees off the surgeon with the words “… famous after they’re dead”.