Gene gold turning to dust?
Governments are sinking further billions into genomics and related research but a new study finds no sign of revolution in healthcare.
Governments are sinking further billions into genomics and related research but a new study finds no sign of revolution in healthcare Dr. Mae-Wan Ho
Over the past decade, consultants, policy makers, academics and industrialists have united in telling the world how biotechnology, and genomics in particular, are "revolutionizing" drug discovery and bringing about radical changes in healthcare involving predictive and even personalized medicine. These euphoric expectations underpin science and technology policy not only in the rich countries of the OECD and the European Union, but also some of the less rich countries such as Malaysia (see "Biotech fever grips Asia" SiS 16).
UK’s Prime Minister Tony Blair had described the human genome map as "a revolution in medical science whose implications far surpass even the discovery of antibiotics"; and said his government had made available an extra £100 million in 2003 to speed the introduction of new drugs, and would boost investment in research.
But a study on the impact of biotechnology on medical treatments published at the end of 2004 concluded that the objective evidence provides no support for the idea of a biotechnology revolution, and warned of "substantial mismatch between the real world and the unrealistic expectations of policy-makers".
The tens of billions invested produced only a handful of useful drugs over the past 20 years; and despite a 10-fold increase in research spending worldwide, the total number of new drugs has remained virtually unchanged.
The scientific "breakthroughs" have been equally disappointing: Dolly the cloned sheep was supposed to bring identical "elite herds" as ‘bio-factories’ for pharmaceuticals; but the cloning process proved extremely difficult. Dolly became seriously ill and had to be put down, extinguishing any hope of animal pharming (see "Animal pharm folds" SiS 19).
Dolly’s creator Ian Wilmut gave up cloning animals (see "Death sentence on cloning", SiS 19). He applied instead to the Human Fertilisation and Embryology Authority (HFEA) and was awarded a licence to clone human embryos for stem cells research, holding out hope of curing diseases by embryonic stem cell transplant.
But there is little moral or scientific justification for such ‘therapeutic’ human cloning, especially given the technical difficulties of the cloning process and the known risks in using embryonic stem cells for transplant, in contrast with the proven successes and promise of adult stem cells that can easily be obtained from patients requiring the transplant (see "Human cloning & the stem cell debate", SiS 16).
The clinical successes of the patient’s own adult stem cells have been amply confirmed recently (see "Which stem cells" series, SiS 25), at the same time that the technical, economic, safety and ethical concerns over embryonic stem cell have multiplied (see "No case for human embryonic stem cells research", SiS 25).
Gene therapy has yet to cure any person of major genetic disorders such as cystic fibrosis or sickle cell anaemia. To-date, nine children with X-linked severe combined immune deficiency had apparently been successfully treated, by re-implanting the patient’s bone marrow cells that were genetically modified in the lab. But three of the treated children have developed leukaemia; and the full risks of gene therapy are coming to light.
Gene therapy vectors provoke immune reactions that target viral gene products, transgene products as well as plasmid DNA (see "Gene therapy woes" this series). It was an acute immune reaction that killed a healthy teenage volunteer in a gene therapy clinical trial in 1999 (see "Failures of gene therapy", SiS 16). Five years later, serious safety concerns have emerged over a new gene therapy technique hailed as a breakthrough in 2002 (see "Controversy over gene therapy breakthrough", this series).
Mapping the human genome and the enormous expansion in ‘bio-informatics’ brought little in the way of miracle cures or wonder drugs. In October 2004, another draft of the human genome map was announced; and we are told it is only "the end of the beginning". But even that is not certain; for the new genome map, though much improved in accuracy, is still not complete. The ‘finishing’ procedure roughly doubled the total time and cost of the human genome project. And a lot more investment is necessary to really bring about the revolution in healthcare. ‘Health genomics’ is indeed in danger of being the "financial and scientific black hole" I had predicted five years ago.
Paul Nightingale from the Science Policy Research Unit, University of Sussex, and Paul Martin from the Institute for the Study of Biorisks and Society, Nottingham, looked at relevant indicators that might support the idea of there being a biotechnology revolution.
The explosive increase of scientific publications in genomics between 1978-2002 clearly indicated a major, and possibly revolutionary, change in some of the scientific inputs that may lead to drug discovery. But data from the US Patent Office (USPTO) in the same period showed only a steady rise in the number of patented compounds. Patenting increased approximately seven-fold, while R and D spending increased roughly ten-fold.
So, even if one takes into consideration the expected lag of 4–8 years between R and D investments and patenting, there is no evidence of dramatic improvement in drug discovery. On the contrary, there is a decline in R and D productivity as measured by the number of patents per dollar spent on R and D, and hence, a possible decline in research productivity, at least in the short term.
Several other indicators followed the same trend.
The number of drugs approved by the FDA in the period 1983–2003 showed an increase until the mid 1990s, followed by a sharp decline, so that roughly the same number of drugs was approved in 2002 as two decades earlier. Set against the substantial increase in R and D expenditure that took place between 1970 and 1992 (i.e. allowing for the 8–12 year lag between research investment and new product launches) there is further evidence of a decrease in productivity rather than the revolutionary increase we have been told to expect.
In terms of therapeutic proteins and antibodies that have reached the market since 1980 and sold more than $500m a year in 2002 and 2003, there are only 12 recombinant therapeutic proteins and three monoclonal antibodies. Moreover, three of the therapeutic proteins were already characterized in 1980, with biotechnology simply leading to new production techniques.
Other researchers in Edinburgh University and the Open University using data that evaluate the performance of new drugs, found only 16 drugs evaluated between January 1986 and April 2004 that were better than ‘minimal improvements’ over pre-existing treatments.
In short, the evidence provides no support for a biotechnology revolution.
"The emergence of the biotechnology industry has rested heavily on the creation of these high hopes and many people in the sector have been active in promoting the idea of a biotech revolution." Nightingale and Martin wrote, "Management consultants, financial analysts and venture capitalists all clearly have a vested interest in hyping new technologies. Similarly, the promise of a biotechnology revolution provides government policy makers with simple, but as our analysis suggests, probably ineffective ways of promoting regional development, improved healthcare delivery and economic growth."
Nightingale and Martin continued: "Unrealistic expectations are dangerous as they lead to poor investment decisions, misplaced hope, and distorted priorities, and can distract us from acting on the knowledge we already have about the prevention of illness and disease."
We remain caught in the biotechnology bubble created around the scientific myth of genetic determinism that was untenable even before the human genome was mapped, and thoroughly exposed as such since then. The vast domains of complexity that connects the genome to the rich tapestry of life are refusing to yield to mechanistic analysis ("Biotech wonder tool in disarray", this series). But the scientific establishment and our policy-makers lack the moral and intellectual courage to admit that to themselves or to the public. So, governments continue to sink billions of taxpayer’s money into raising false hopes of gene therapy and personalized medicine and putting society at risk from eugenics. This money can be much more effectively invested instead to address the real causes of ill-health, which are overwhelmingly social and environmental ("Why genomics won’t deliver", this series).
Article first published 21/03/05
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