Update on Life Issues - October 2013
An unprecedented nexus
Never before has there been such manifold evidence that the Abortion Act 1967 is being abused. The Department of Health, the Care Quality Commission (CQC), the police and the Crown Prosecution Service (CPS) need to act without delay to ensure the law is being obeyed. This novel nexus of serious non-compliance consists of three strands.
First, in February 2012, as a result of undercover investigations by journalists from The Daily Telegraph there was the revelation that sex-selective abortions were being performed in the UK – unborn girls were being preferentially aborted. Such abortions are considered to be illegal. Jeremy Hunt, the Health Secretary has said, 'We are clear that gender selection abortion is against the law and completely unacceptable.' In July 2012, the Department of Health and the CQC launched an inquiry only to conclude that no such practices were occurring in the UK. Then, after its own 19-month inquiry, the CPS decided not to charge the two accused doctors, despite it admitting that there was sufficient evidence to proceed, but that such prosecutions would not be ‘in the public interest’. Eventually, on 7 October, the Director of Public Prosecutions, Keir Starmer, published a detailed explanation for this inaction by the CPS. Its wriggle was based on the fact that there was no victim in these cases because the abortions did not proceed. Moreover, the DPP admitted that although gender selection alone cannot be a ground for abortion, such abortions are not necessarily unlawful. For instance, the British Medical Association (BMA) guidance for doctors states, ‘It is normally unethical to terminate a pregnancy on the grounds of fetal sex alone.’ However, the BMA guidance continues, ‘The pregnant woman’s views about the effect of the sex of the fetus on her situation and on her existing children should nevertheless be carefully considered.’ In other words, Ground C of the 1967 Act can be used as a catch-all reason for sex-selective abortions. Let’s face it – there are no reasons for disallowing any abortion in Great Britain. We effectively have ‘abortion-on-demand’. Though we berate India and China for their ghastly policy of aborting unborn girls, we are conveniently blind to our own practices. The upshot of this tangled affair is that instead of prosecution, the CPS is happy that the two doctors, Dr Prabha Sivaraman, who worked at the North Manchester General Hospital and a private abortion clinic in Manchester and Dr Palaniappan Rajmohan from the Calthorpe Clinic, Birmingham, will face an inquiry by the General Medical Council, which has the power to strike them off the medical register. I wonder if it will.
Second, the same newspaper stings showed that doctors, at least in 14 hospitals across England, were routinely pre-signing, and even photocopying, the abortion consent form, known as HSA1. The level of abuse is staggering. For example, at Rochdale Hospital all the forms were pre-signed. At the Princess Alexandra Hospital, Harlow the same photocopied signature was used even after the doctor had left the Hospital’s employment. Furthermore, it has become clear that some women were having abortions without ever being seen, let alone examined, by even one doctor. Yet, as the NHS website states, ‘Before an abortion can proceed, two doctors must ensure that the requirements of the Abortion Act are fulfilled, and they must both sign the relevant certificate.’How can these medical practitioners claim to be acting ‘in good faith’, as the 1967 Act specifically requires, and discharging their duty of care towards these patients?
Third, in November 2011, the Royal College of Obstetricians and Gynaecologists published its updated guideline, The Care of Women Requesting Induced Abortion, and stated (p. 45) that, 'Women with an unintended pregnancy should be informed that the evidence suggests that they are no more or less likely to suffer adverse psychological sequelae whether they have an abortion or continue with the pregnancy and have the baby.' And in December 2011, the National Collaborating Centre for Mental Health at the Royal College of Psychiatrists published a large-scale review of the relevant literature entitled, Induced Abortion and Mental Health. It stated (p. 8) that, 'The rates of mental health problems for women with an unwanted pregnancy were the same whether they had an abortion or gave birth.' Together these two high-ranking publications declared categorically that the continuation of a pregnancy does not involve risk of injury to the mental health of the pregnant woman, greater than if the pregnancy were terminated. In other words, abortion is never the better option. This was a bioethical thunderbolt. Seemingly, 99.96% of the abortions performed under ground C for mental health reasons – about 98% of all UK abortions, accounting for well over 180,000 – are outside the provisions of the 1967 Act and are therefore illegal. If so, they are crimes under the Offences Against the Person Act 1861.
Here is the big question – has a coach and horses been driven through the Abortion Act 1967, year after year? We need the answer. The authorities need to provide it. Or is there a fear that the answer would expose the whole sordid truth that ‘abortion-on-demand’ and contempt for the law have become the abortion industry’s custom and practice? Much now depends upon Parliament and in particular the members of the All-Party Parliamentary Pro-Life Group (APPLG) – step up one brave MP and bring this debacle before the whole House. Already, on 9 October, David Burrowes, MP for Enfield Southgate, brought forward a debate in Westminster Hall on the workings of the 1967 Act. It forced the Attorney General, Dominic Grieve, to attend and concede that the 1967 Act’s provisions are unclear and that the Department of Health, the CQC and the DPP will issue clearer and more specific guidance for both doctors and prosecutors. We shall be waiting and watching.
Parliamentary Inquiry into Abortion on the Grounds of Disability
This important Inquiry, chaired by Fiona Bruce MP, centred on Section 1(1)(d) of the Abortion Act 1967, whichsets no time limit on when an abortion may take place if, ‘there is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped.’ This is commonly known as Ground E of the Act.
Members of the Inquiry took oral and written evidence from a total of 299 individuals and organizations, including Affinity, and produced a list of 17 recommendations. The latter included more support and information for parents with a new diagnosis of a suspected disability in their unborn child, more funding for neonatal palliative care, better training for health professionals dealing with prenatal diagnosis, and a welcome emphasis on adoption as a positive alternative to abortion for disability. In addition, there was a call for post-mortems for abortions conducted after 24 weeks to ensure the correct operation of the Act and to improve future medical diagnoses.
The Inquiry’s most robust and radical conclusion was, ‘We recommend that Parliament reviews the question of allowing abortion on the grounds of disability and in particular how the law applies to a fetus beyond the age of viability (currently 24 weeks). Parliament should consider at the very least the two main options for removing those elements which a majority of witnesses believe are discriminatory – that is either reducing the upper time limit for abortions on the grounds of disability from birth to make it equal to the upper limit for able bodied babies or repealing Section 1(1)(d) altogether.’
The Inquiry has highlighted significant anomalies and discriminations concerning Ground E abortions. The hope is that Parliament will be alerted to act, or will it be content to bury the evidence?
Abortion in the Republic of Ireland
This new Act was introduced largely as a result of legal ambiguity surrounding the tragic case of Savita Halappanavar, a 31-year-old Indian dentist, who was admitted to hospital in Galway in October 2012. She was miscarrying and her request for an abortion was refused because her life was not in danger. She died a week later from septicaemia.
This landmark change in Irish law has not been part of the democratic process. The government was determined to pass the Bill and many Fine Gael, Labour and Sinn Fein politicians were left with no choice but to vote against their conscience or lose their jobs. Some of these politicians had even made pre-election promises to their electorate not to support any legislation which would introduce abortion into Ireland. 30 July 2013 was indeed a sad, sad day for Ireland.
A ‘once-a-month contraceptive pill’
Of course, any such monthly-pill would not be a ‘true’ contraceptive, but rather a post-fertilisation method that could act as an abortifacient. Indeed, as the authors recognised, ‘Although such methods would displease abortion opponents, they would likely be welcomed by many women. Research to develop post-fertilisation fertility control agents should be pursued.’
And that was all this article called for, ‘research’. But if the hype and enthusiasms of the media were to be believed, such ‘a monthly-pill’ was here already, or just around the corner. Yet prototypes exist in the form of so-called emergency ‘contraception’ – the morning-after and week-after pills, Levonelle One Step and ellaOne, can operate as abortifacients for up to 3 and 5 days respectively after unprotected sexual intercourse. And there is a similar drug, mifepristone (RU-486), which is regularly used in the UK to procure medical, as opposed to surgical, abortions.
But have these authors thought about the implications of a ‘once-a-month’ pill? What about women’s greater risks to sexual abuse? Already girls and women have few enough reasons to say, ‘No.’ And what about the lack of protection from sexually-transmitted infections? Their incidence is already spiralling out of control. And what about the dangers to women’s health? Stockpiling such a pill, its frequent consumption and its unknown long-term adverse effects seem unimportant to these authors. Their primary aim seems to be the procurement of early abortions – any how, anywhere, any woman.
Assisted Reproductive Technologies‘Three-parent’ IVF
But this is just the entrée. You know it will not stop there, it never does with bioethical issues. Once permitted, ‘three-parent’ IVF will be used not only to treat or prevent disease, but rather to fulfil lifestyle desires. For example, it could assist polyamorous threesomes or lesbian couples to have children biologically related to all partners involved.The designer baby
The pan-European ‘One of Us’ initiative
Having reached the all-important million votes, the leaders of the ‘One of Us’ initiative will now be granted an official public hearing in the European Parliament to outline the need for legislation, and they are guaranteed a formal response from the European Commission.
The initiative’s timing is crucial because negotiations are currently underway for Horizon 2020, the EU’s research funding programme for the period 2014 - 2020. This is only the second petition to meet the requirements of the European Citizens’ Initiative (ECI) since the EU adopted the scheme in February 2011 to increase democratic participation in its activities. At least a million people have spoken – the outcome will be interesting.
A heart-warming story
The couple were eventually selected by a pregnant mother – they met and bonded. When Sarah accompanied the mother for an ultrasound scan, there was a shock – she was carrying triplets! A few months later, Joel, Hannah and Elizabeth were born and welcomed into the Justice family. But that is not the end. Just one week after the triplets were born, Sarah found out she was pregnant – with twins! Sarah and Andy are now expecting a girl and boy this coming January. From 0 to 5 in a year.
The three lessons. The couple wanted children – good desire. The couple turned from IVF to adoption – good choice. They helped a pregnant mother – good deed.
A less than heart-warming story.
You will not believe this
As the research leader, Yuanyuan Zhang said, ‘These cells can be obtained through a simple, non-invasive low-cost approach that avoids surgical procedures.’ It is thought that these stem cells probably originate from the upper urinary tract, including the kidneys.
These urine-derived stem cells (USCs) were collected from seventeen healthy individuals ranging in age from 5 to 75 years, and subsequently differentiated into smooth muscle-type cells, like those that line the inside of the urethra and bladder. And furthermore, once attached to bioscaffolds, these USCs could be coaxed to become connective tissue and blood vessels, with the potential to become bone, muscle, nerve or adipose cells.
These are very preliminary results, but still fascinating. And the approach has been corroborated by Chinese scientists in the July edition of Stem Cell Regeneration. Their work, published as Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells, generated tooth-like structures from human urine induced pluripotent stem cells (ifhU-iPSCs). They first collected USCs, differentiated them into ifhU-iPSCs, cultured them into epithelial sheets, which were then recombined with mouse dental connective tissue, which differentiated into enamel-secreting cells in tooth-like structures, which possessed physical properties similar to those found in normal human teeth. The expectation is that one day, this technology will allow the regrowth of lost teeth in human patients. Can you believe it?
You will perhaps believe this
The team took living tissues from cows and sheep and grew them on a flexible titanium wire frame that had the three-dimensional shape of a real human ear. This was then implanted onto a rat with a suppressed immune system to allow growth to take place. This is a significant advance in tissue engineering and the hope is that one day, replacements ears will be grown from patients’ own stem cells. If so, it will be a boon for people born with malformed ears, or who have lost them in accidents.
But you will probably not want this
And the taste? An Austrian food researcher, Hanni Ruetzler said, ‘I was expecting the texture to be more soft ... there is quite some intense taste. It's close to meat, but it's not that juicy. The consistency is perfect, but I miss salt and pepper.’ And a US food writer, Josh Schonwald said, ‘The mouthfeel is like meat. I miss the fat, there's a leanness to it, but the general bite feels like a hamburger. What was consistently different was flavour.’
Professor Post claimed, ‘… we are going to present the world's first hamburger made in a lab from cells. We are doing that because livestock production is not good for the environment, it is not going to meet demand for the world and it is not good for animals.’ The extremist animal welfare campaigning group, People for the Ethical Treatment of Animals (Peta), predicted that, ‘[Laboratory-grown meat] will spell the end of lorries full of cows and chickens, abattoirs and factory farming. It will reduce carbon emissions, conserve water and make the food supply safer.’ Yet, with an inexorably growing global demand for meat and the cost of this burger estimated to be £215,000, none of these prospects seems either logical or practical.
Embryonic stem-cell (ESC) progress
First, the on-going work by a team at Moorfields Eye Hospital and University College London has demonstrated that the part of the eye which actually detects light can be repaired using embryonic stem cells. Experts eagerly, and perhaps over-excitedly, described this as a ‘significant breakthrough’ and a ‘huge leap’, which will make human trials ‘a realistic prospect’.
The work was published in the July edition of Nature Biotechnology under the title, Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Itdemonstrated, ‘… unequivocally that ESC-derived photoreceptor precursor cells have the capability to integrate and mature to form outer segments and synaptic connections after transplantation into the degenerate adult mouse retina.’ Well, yes, but it was only in mice. And only 1 in 200 ESCs were incorporated into the rest of the eye. And treatments for several eye diseases using adult stem cells have already been tested and proven to be effective.
Second, there has been the rather spooky use of human ESCs to grow so-called miniature brains or organoids, spherical structures about four millimetres across, but reckoned to be equivalent to those of a nine-week-old foetus. The project’s rationale is to model neurological development and disorders, such as microcephaly, schizophrenia and autism.
This work has been led by Dr Juergen Knoblich at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences in Vienna together with scientists at the University of Edinburgh. They used both ESCs and, perhaps more significantly, iPS cells derived from human skin cells. The results were published in the September edition of Nature under the title, Cerebral organoids model human brain development and microcephaly.
Differentiation of stem cells into bone, heart, blood and nerve cells is one thing. Differentiation into human mini-brains is quite another. These little pea brains had a tiny cerebral cortex and even the beginnings of eyes as well as the nervous connections and the electrical impulses that are essential for functional communication. It opens up serious questions of what constitutes a person, what is the mind, consciousness and awareness? And what about the creation of more mature cerebral organoids? This combination of using ESCs and creating mini-brains somehow seems doubly sinister.
Induced pluripotent stem (iPS) cell progress - I
The work headed by Jacob Hanna and his colleagues was published in the September issue of Nature with the title Deterministic direct reprogramming of somatic cells to pluripotency. It was shown to occur with both mouse and human cells. This new technique should allow the production of larger volumes of stem cells and therefore hasten the development of new, potential treatments for humans.
Induced pluripotent stem (iPS) cell progress - II
Hongkui Deng and his team at Peking University in Beijing began to screen 10,000 small molecules to find chemical substitutes for the Oct4. After years of searching they found that mouse iPS cells could be generated by the addition of a combination of seven small-molecule compounds, rather than any genes. Their findings have been published as Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds in the July copy of Science.
This chemical reprogramming strategy makes the use of iPS cells even more attractive for safe, human clinical applications.
Induced pluripotent stem (iPS) cell progress - III
These scientists managed to create functional human livers from human iPS cells by transplantation of liver buds created in vitro. These liver buds remarkably organized themselves into liver tissues that could perform mature liver-specific functions, such as protein production and drug metabolism.
This is the first report of the generation of a functional human organ from iPS cells. Of course, treatments for patients are some years in the future, but this is a crucial proof-of-concept demonstration that organ-bud transplantation could become a new and promising approach for regenerative medicine.
The return of the fear of reproductive cloning
Indeed, that fear has been heightened by research from Japan.Katsuhiko Hayashi of Kyoto University has managed to harvest skin cells from mice, transform these into primordial germ cells (PGCs), which can then develop into both sperm and ova. He has already used them reproductively to produce live mice. And that is not all. Hayashi’s work raises the possibility of creating fertilizable ova from the skin cells of infertile women. And that is not all. Perhaps men's skin cells could be used to create human ova. And women’s skin cells could generate human sperm. Already Hayashi has received dozens of requests from infertile couples, as well as lesbians and gays, to help them achieve their dream – a baby.
Of course, the transition from mice to monkeys to humans is a long and winding road, but this formidable journey has now started. One huge hurdle is the unlikelihood of creating ova from male XY cells and sperm from female XX cells. But, as scientists are learning to say, ‘Never say soon, but never say never’. For the rest of us, now is the time to begin to grapple with these novel bioethical issues.
News from the USA
The Hobby Lobby saga – still fighting
Back in September 2012, Hobby Lobby’s CEO, David Green and his family, filed a suit claiming that portions of the Affordable Care Act infringed their religious liberties by forcing it to pay for health procedures that cause abortion.
The saga has recently been ratcheted up a notch. The Obama administration has now asked the Supreme Court to review Hobby Lobby’s lawsuit against the Department of Health and Human Services (HHS). The crafts retailer has until 21 October to file a response to a 251-page appeal by the US Solicitor General.
The HHS mandate requires the family-owned business to provide full contraceptive cover or pay $100 per day for each of its employees, that is, about $1.3 million per day in fines. For the moment the Green family have a temporary injunction excusing them from paying these penalties. If the US Supreme Court agrees to hear the case, oral arguments could begin in early spring, and a decision could be made as early as June 2014.
The battle across the states
However, the Center for Reproductive Rights promised a court challenge even before the Governor’s ink was dry. And on 22 July, District Judge Daniel Hovland granted a temporary injunction – he ruled that the new law was ‘clearly unconstitutional’. He wrote, ‘The United States Supreme Court has unequivocally said that no state may deprive a woman of the choice to terminate her pregnancy at a point prior to viability.’
During the summer months, similar pro-life laws restricting access to abortion were enacted in states, such as Alabama and Wisconsin. However, legal challenges rapidly followed and judges swiftly issued temporary injunctions against most of their stipulations. Similarly, in Mississippi, a judge allowed one such legal proviso to go into effect, but barred others from penalizing the state's only abortion facility.
Yet some such pro-life bills have survived intact. For example, on 1 October, a new North Carolina abortion law came into effect. It restricts insurance coverage of abortions – except in cases of rape, incest or medical emergency – it prohibits sex-selective abortions, it requires doctors to be present for the entire abortion procedure, it sets new standards that abortion clinics must meet in order to continue in business and it allows any care worker, not just doctors or nurses, to opt out of performing abortion procedures.
The required health and safety upgrades mean that several of North Carolina’s sixteen abortion clinics will need to make costly alterations to bring their facilities up to the new standards, or be forced to close.
Overturning Roe v. Wade
Now comes news that some political commentators think that the Supreme Court will review the abortion-providing, legal monolithic decision of Roe v. Wade within the next two years. For example, American University political science professor Karen O'Connor, who supports abortion-on-demand, has recently told ABC News, ‘I think we are going to see Roe overturned. I’m thinking 2015.’ She considers that the number of cases ‘pending in the circuit courts’ makes it more likely the justices will take up a challenge to Roe.
Moreover, she senses that people no longer believe that viability – set by Roe v. Wade as 28 weeks, but later revised to 24 weeks – is the only criterion that should limit when a woman can procure an abortion. A majority of people now consider that abortion should not be allowed if the child is capable of feeling pain, which, according to some experts, could be no later than 20 weeks. Bills forbidding abortion after that point have already been passed in 13 US states as well as in the US House of Representatives. Furthermore, there has been a public outcry over the trial of Kermit Gosnell and his ‘House of Horrors’ abortion facility, in addition to the gruesome practices of other late-term abortionists – these have helped change public opinion. And according to Peter Hoffa, American history professor at the University of Georgia, ‘There are four members [of the nine] of the Court now who feel that Roe v. Wade was wrongly decided.’
Is the stage being set for a showdown? And if Roe v. Wade falls ……
Euthanasia and Assisted Suicide
Liverpool Care Pathway for the Dying Patient (LCP)
The question is, what will replace it? It is not as if there is some wonderful, untried system of end-of-life care waiting to replace it. The basic building blocks of proper palliative care are already known and implemented in many places.
According to Norman Lamb MP, Minister of State for Care and Support, the LCP will be replaced by ‘… a personalised care plan backed up by condition-specific good practice guidance and a named senior clinician responsible for its implementation.’ The 61-page review with its 44 recommendations is a decent bureaucratic start, but it will not be effective unless good training, adequate resources and a staff commitment are its practical foundations. We shall see.
Euthanasia and assisted suicide in the courts
That might have been regarded as the end of the matter as far as challenges via the courts were concerned. But not so. Along came the case of Paul Lamb, a 57-year-old former lorry driver from Leeds, who has been almost completely paralyzed for the last 23 years after a road accident. He apparently suffers constant pain and describes his life as, ‘tedious, monotonous and pointless.’ But he is not terminally ill and therefore the folk from the Dignity in Dying organisation stay away from his case because it is beyond their advocacy remit.
Paul Lamb was given permission to join the anonymous man known as ‘Martin’ in the continuing legal battle initiated by Tony Nicklinson in the hope of asking a doctor to end their lives. However, on 31 July 2013, their case was dismissed by the three judges at the Court of Appeal. In other words, their challenge to change the law on murder was rejected. But Martin’s case was partially upheld, by a 2 to 1 judgement. The Director of Public Prosecution (DPP) was ordered to clarify the role and the degree of support that healthcare professionals could provide for their clients before prosecutions were likely, an example of the so-called class two cases. The DPP is expected to appeal this decision at the Supreme Court this autumn.
The three cases of Nicklinson, ‘Martin’ and Lamb are tragic and we must all be moved with compassion for them. But the simple truth is this – current laws exist to protect the vulnerable, the disabled, the terminally-ill and all elderly people. Any changes to the Suicide Act 1961 or the Murder Act 1965 would expose such people to greater burdens and considerable coercion, which might lead to their wishing to end their lives prematurely.
The Falconer and MacDonald Bills
The assisted suicide battle continues
The most recent celebrity to come out in favour of some sort of euthanasia is Britain’s most famous scientist, Professor Stephen Hawking. The 71-year-old cosmologist parroted that old adage so beloved of pro-euthanasia people, ‘We don't let animals suffer, so why humans?’ In the past he has said, ‘While there's life, there's hope.’ Now he seems to have changed his mind.
And, as if that super-intelligent man’s support is insufficient, then ITV’s most popular soap opera, Coronation Street, is about to tackle the big issue. Apparently, the terminally-ill character Hayley Cropper, who has been diagnosed with inoperable pancreatic cancer, decides she wants to take control of her death. According to the grapevine, both sides of the right-to-life debate will be aired as her screen husband, Roy, is strongly opposed to her decision. We can only hope that ITV is less of a supporter of assisted suicide than the BBC has proved to be.
Gene therapy – a happy ever after story
Gene therapy appears deceptively simple – trim off a rotten section of the patient’s genome and replace it with a good piece. It is a bit like repairing a leaking pipe in a central heating system. Only it is not.
This story is about somatic gene therapy, the bioethically-acceptable sort, not germline gene therapy, the nasty eugenic sort. The first approved clinical trial of somatic gene therapy started in the USA in September 1990. The target disease was severe combined immunodeficiency (SCID) and the patient was four-year-old Ashanti DeSilva. The treatment worked, almost. But the following two decades of gene therapy were disastrous, patients died and some contracted cancers. The Cinderella of medicine became an ugly sister – we were promised a crock of golden cures, we got a can of deadly worms.
After twenty and more years of anxious effort, lessons have been learned, techniques honed and more circumspect approaches adopted. There has been a decade of hushed achievement, and now gene therapy is back in the news. A cautious optimism has returned as typified by the results from two important trials published over the summer in the journal Science. The researchers were mainly Italiansworking at the San Raffaele Telethon Institute for Gene Therapy in Milan and the papers’ titles were Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy and Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome.
Both studies used lentiviral vector transduction. This involves the collection of a type of stem cell from the body, adding some good, therapeutic genes using a delivery system (or vector), which has been safely tweaked from some HIV components, and putting the modified cells back into the patient. Lentiviral vectors have been previously used to treat patients successfully in France with the diseases adrenoleukodystrophy and β-thalassaemia. The Science papers reported the results of trials for two more life-threatening diseases. First, metachromatic leukodystrophy (MLD), a genetic disease that affects lipid metabolism is caused by a lack of the enzyme arylsulphatase A (ARSA) and affected children can die within a few years. Second, there is Wiskott–Aldrich syndrome, which is primarily a disorder of the blood-forming tissues affecting mainly boys and leading to a defective immune system.
In the first trial, the team collected haematopoietic stem cells from the bone marrow of three children with MLD. These blood-making cells were exposed to an ARSA lentiviral vector and the altered cells transfused back into the young patients who had previously received a course of chemotherapy to suppress their immune systems. This treatment is known as autologous transplantation with myeloablative conditioning. The expectation is that the new, ‘corrected’ cells would supply the missing ARSA enzyme. Indeed, even after two years, more than 60% of the blood cells expressed ARSA concentrations ten times that of normal. The disease was arrested in all three patients. They now attend school.
In the second trial, a similar approach was taken but with less myeloablation and more immunosuppression. Nevertheless, it too worked with between 25 and 50% of the blood cells expressing the lentiviral vector.
Why the successful outcomes? First, the lentiviral vectors are a vast improvement on previous vectors used in gene therapies. Second, both trials used relatively high concentrations of these vectors, and they are potent, easily purified and adaptable. Moreover, the lentiviral vectors showed no signs of activating cancer genes as their predecessors had done.
Somatic gene therapy is, at last, delivering the promised goods. However, it is also now clear that gene therapy, even withits vast positive potential, will not provide many magic bullets – the majority of human genetic disorders are far too complex. Trying to tackle and correct them with current gene-therapy methods would be foolhardy. Today’s gene-therapy procedures are too specialized, too labour-intensive and too expensive. Nevertheless, these one-off gene therapies compared with the lifelong cost of enzyme replacement or small-molecule treatments could become more attractive. Yet future gene therapies will have a major impact only when vectors, which carry the altered genes, are developed that can be, for example, safely injected into patients, like some diabetics now use insulin. Only then will an ever-growing range of diseases be treatable, but it will still be for hundreds of patients, maybe thousands, rather than the millions.
Nevertheless, gene therapies are advancing. As a foretaste, the first gene therapy was given marketing authorisation for use in Europe last year and a commercial rollout is expected in late 2013. The product is called Glybera, which is used to treat a deficiency of lipoprotein lipase, an enzyme essential for fat metabolism. The disease can cause abdominal pain and pancreatitis, a life-threatening inflammation of the pancreas. Conventional treatment has been for patients to consume a very low-fat diet. Glybera therapy, developed by UniQure, uses a virus to infect muscle cells with a functioning copy of the faulty gene. Glybera is administered via a one-time series of small intramuscular injections in the legs. And it works – clinical trials decreased fat concentrations in blood and reduced the occurrence of acute pancreatitis episodes. The ugly sister is looking more like Cinderella.