Insight and Foursight: Is there gold in them there hills?

This is a guest blog from Richard Egan filling for Dr David Van Gend who is enjoying a well earned break.

As the debate on Kay Patterson’s cloning bill draws closer the pro-cloning lobby are once again pulling out all the stops in their hyped up claims for the promise of therapeutic cloning.

The Insight program on SBS featured paraplegic Brock Turner and a young man, James Shepherd, with juvenile diabetes, making emotional pleas to allow cloning in order that Brock could walk again and James go to sleep at night without the fear of never waking up. Who would dare deny them hope?

Never mind that as, Emeritus Professor Jack Martin, pointed out there has been no proof of concept of the safety and efficacy of therapeutic cloning in any animal model.

Never mind, as James Sherley**, Associate Professor of Biological Engineering at MIT, who is currently visiting Australia said “The unique feature of embryonic stem cells that allowed them to turn into any cell of the body, known as pluripotency, created a problem when researchers injected them into tissue.

“When you put them in an environment where they can grow and develop, they make lots of different kind of tissues. This tumour formation property is an inherent feature of the cells.

“And all you have to do is simply inject them into an animal tissue – this happens at very high efficiency.

“And although some might say we can solve the tumour problem down the road, that's equivalent to saying we can solve the cancer problem and we may, but that's a long time coming.”

Never mind, as Professor John Burn, medical director of the Institute of Human Genetics at the University of Newcastle upon Tyne, admitted when pressed on the Insight program, that neither his institute, which holds one of the two British licenses to create human embryo clones, nor anyone else in the world has yet produced a human blastocyst by somatic cell nuclear transfer, let alone derived embryonic stem cells from a human embryo clone.

The same Professor Burn assures us cheerfully that the would-be cloners have “gold nuggets in their pockets” as they come down from there hills!!

Similarly, Dr Graham Mitchell and Sir Gustav Nossal, trading as Foursight Associates Pty Ltd, a company in strategic alliances with JBWere Private Equity Fund, Challenger Biotech Capital Ltd and KPMG Melbourne, claim in their report to Premier Steve Bracks and Victorian Minister for Innovation, John Brumby that: “a broad SCNT approach is required for stem cell-based regenerative medicine to achieve its undoubted promise.”

The Foursight report mentions three hurdles to using embryonic stem cells for therapies. These are (a) transplant rejection; (b) guidance of the ES cells down the correct pathways of differentiation and (c) ensuring that cells of such great proliferative potential do not develop into cancers, even on rare occasions.

The Foursight report breathlessly proposes SCNT (cloning) as the way to overcome the transplant rejection hurdle:

“If transplant rejection is the biggest single concern then this is where the extraordinary, legislatively-constrained technology of SCNT – somatic cell nuclear transfer- comes into its own. Clearly, SCNT has the potential to overcome the transplantation barrier through “personalization” of the ES cells.”

The Foursight report fails to address the other two hurdles or to explain what possible reason there is to lift the legislative ban on cloning now before these hurdles are overcome in animal models. What is the point of being able to do stem cell transplants that won’t be rejected but cannot be reliably differentiated into the required cell types and have a tendency to form cancers?

The Foursight report also glosses over a fourth hurdle, the problem of abnormalities in genetic coding, referring to two papers demonstrating equivalence between mouse ESCs from cloned mice with those from fertilised mice. However, given the very evident problem of abnormal genetic programming that is a feature of reproductive cloning of animals, proof that programming and epigenetic effects do not occur in SCNT-derived cell lines will require much more work than this, including especially study of expression of a very much wider array of genes.

The Foursight report is a brief attachment to a longer report, the Gough report, prepared by Dr. Nicholas Gough of Nick Gough & Associates Pty Ltd, biotechnology consultants with a declared interest of holding options to acquire ordinary shares in the Singaporean stem cell company ES Cell International Pte Ltd.

The Gough report admits that “Whilst generation of personalised ES cells by SCNT for specific patient is a theoretical option, given the high costs and length of time involved, it is unlikely that production of personalised therapeutic tissues by genomic replacement would represent a practical strategy.”

There you have it.

In other words, the hyped up hope being offered to Brock Turner and James Shepherd, of therapies for spinal cord injury and for juvenile diabetes using stem cells derived from human embryo clones made using their own somatic cell nuclei is “not a practical strategy”.

Rather, according to the Gough report, hope lies in producing “a bank of some 150 human ES lines [that] could provide a beneficial match for 25 to 50% of potential recipients in a target population (and a 95% chance of providing a full match for at least 8% of patients”. [Such a bank could be developed under Australia’s existing law only no-one has got ESCs to work safely and efficaciously yet.] Oh, and in other ways, yet to be discovered, of overcoming the transplant rejection hurdle.

There is thus a blatant contradiction between the two parts of this hybrid report that has led Premier Bracks to claim “While there is much to do and the road in curing these diseases is a long one it is clear from this report that our greatest roadblock is our scientists’ inability to perform this work [cloning] in human cells in Australia” and his Minister for Innovation, John Brumby to claim that “SCNT remains the only tool available that can create ‘tailored’ stem cells that would be a genetic match to a patient.”

The Foursight part of the report claims that cloning will overcome the transplant hurdle but the Gough report, whose comprehensive literature review and analysis has informed the views of the Foursight team of Mitchell and Sir Gus, states that “it is unlikely that production of personalised therapeutic tissues by genomic replacement would represent a practical strategy.”

The Gough report really only commends cloning as a means to “allow the generation of ES cells derived from individuals with specific genotypes for dissection of complex multigenic diseases, such as Alzheimer’s disease, motor neurone disease, and others of unknown cause or multigenic origin. The ability to generate specific differentiated progeny cells that express aspects of a disease phenotype from ES cells of defined genotype will be invaluable in dissection of such diseases.”

Minister Brumby picks up on this alternative purpose for cloning – the only “practical” use according to the Gough report – in his statement that “SCNT remains the only tool available that can create ‘tailored’ stem cells that … would help to model diseases for drug discovery.”

This completely ignores the still unanswered and seemingly unanswerable challenge to the would-be cloners from Professor Alan Mackay-Sim at Griffith University in his submission to the Lockhart Review:

“It is often stated that therapeutic cloning will be required to investigate the biology of certain diseases and to find cures for them by studying embryonic stem cells and their progeny derived from the patients… Therapeutic cloning is a long and laborious procedure that will require donor oocytes and will produce an inexact “copy” of the donor because of the handful of mitochondrial genes passed on through the donor egg. An alternative source of stem cells for these important investigations is provided by adult stem cells. In our lab we already have over 40 adult cell lines derived from persons with schizophrenia, Parkinson’s disease, motor neuron disease, and mitochondrial disease. These are relatively easily obtained, easy to grow in the lab in large numbers and amenable to cell culture studies, gene expression profiling and proteomics analyses. It is probable that such cell lines as these will render therapeutic cloning irrelevant and impractical.”

Mr Bracks has announced that the Victorian Government would convene a Scientific Leaders’ Forum, to be held on Monday October 16, to consider the findings of the report on Scientific Progress in the Embryonic Stem Cell Field. The Premier’s Office has not replied to requests for more details about this Forum. One could no doubt write in advance the script of hype and evasion that the selected invitees will voice in welcoming the report that “there is gold in them there hills”.



** Melbourne blogsters should come and hear James Sherley, Associate Professor of Biological Engineering at MIT speak on Cloning and stem cell research: what we are not being told on Thursday, October 12, 5.30 pm at Prince Philip Theatre, University of Melbourne (Architecture Building, 150m west of Campus Gate 3, Swanston St)

Professor Sherley is a graduate of Harvard University. When the Harvard Review Board voted to allow cloning he wrote:

“A defining feature of our humanity is that we also have the capacity to do the same for others whom we do not know. If the hands of members of the Harvard review board were sensitive enough, they could come to know human embryos better. They could feel that the smallest such embryos, like us, are warm to the touch, that they move as they grow, and they breathe just as surely as we do.”

Professor Sherley has been brought to Australia by Doctors Against Cloning. He is visiting Melbourne after three days briefing Senators and MHRs in Canberra.