August 28th, 2009

Three years ago a 39-year-old American man arrived at the haematology clinic of Berlin’s sprawling Charité hospital. (The venerable Charité, one of the great names in the history of medicine, used to be in East Berlin, but it’s now the brand for the merged university hospitals of the whole city.) He had both leukaemia and HIV; you wouldn’t have given much for his chances. Now he has neither. How?

Since drug therapy was failing on the leukaemia, Dr House Gero Hütter and his patient decided to go for a bone marrow transplant: a dangerous procedure, since it involves killing all the patient’s marrow cells with toxic drugs and starting again from scratch with a donor’s stem cells. It’s pretty risky and doesn’t always work. Then Hütter had a brainwave. Could he do anything about the HIV at the same time? On the list of 80 bone marrow donors in Germany – seriously altruistic people, this isn’t like giving blood – the 61st had a double CCR5 mutation, which apparently protects from HIV infection. (The general frequency in the population is about 1%, so there was no certainty of finding any donor). He carried out the transplant with this donor’s marrow, necessarily stopping the retrovirals; the patient survived and was (for now) free from leukaemia. When Hütter checked for HIV a few weeks later, he found none: and three years later, there still isn’t any. HIV may be lurking somewhere in the man’s system, but if so it doesn’t spread. The man is functionally cured. (Story paraphrased from fine WSJ reporting by Mark Schoofs.)

This amazing news caused a great tizz in the AIDS research community. The treatment as it stands is far too dangerous and impracticable for anybody without the double disease, but it proves that double CCR5 is a portal to a cure. Lots of researchers are now working on less hairy gene therapies. Thees chust might vork.

There’s a qualitative difference between treatments and cures. For one thing, treatments are expensive; cures cheap.

Since he would have done the marrow transplant anyway, the marginal cost of Hutter’s HIV cure was effectively zero. A course of treatment for syphilis in the USA (the test plus penicillin, leaving out the counselling and follow-up) costs $53. It’s almost totally effective, as the spirochaete has no resistance. Barry Marshall’s discovery that many ulcers are caused by helicobacter pylori infection replaced many treatments with expensive drugs like Zantac with courses of cheap antibiotics, though they don’t invariably work. The total cost of guinea worm eradication (Jimmy Carter’s great legacy) is expected to be, from start to finish, $125 million.

It’s not just me saying this. The great cancer researcher and medical writer Lewis Thomas wrote this in 1983 (The Youngest Science, endnote to page 175). The context is his stint as an adviser on health policy in Lyndon Johnson’s White House in 1967:

We recognised three levels of medical technology:

(1) genuine high technology, exemplified by Salk and Sabin poliomyelitis vaccines, which simply eliminated a major disease at very low cost by providing protection against the three strains of virus known to exist;

(2) “halfway” technology, applied to the management of disease when the underlying mechanism is not understood and when medicine is obliged to do whatever it can to shore things up and postpone incapacitation and death, at whatever cost, usually very high indeed, illustrated by open-heart surgery, coronary artery bypass, and the replacement of damaged organs by transplanting new ones…

and (3) nontechnology, the kind of things doctors do when there is nothing at all to be done, as in the case of patients with advanced cancer and senile dementia.

We suggested that the rising cost of health care was resulting from efforts to treat diseases of the halfway or nontechnology class, and recommended that basic research on these ailments be sponsored by NIH.

Thomas’ analysis still looks spot on to me. But his optimism has so far not proved justified: the billions poured into medical research ever since have led to many improved treatments but disappointingly few cures. The ideal state for Big Pharma is represented by the state of the art on diabetes and HIV: costly lifelong treatments. For most lethal conditions, we don’t have even that. Oncologists keep score by five-year survival rates. My wife just beat that, so she goes down in the win column: I suppose I should be grateful.

One reason cancer drugs cost such ridiculous amounts is that they are so ineffective, and will probably be replaced soon by something a tiny bit better. There was a controversy in Britain over Pfizer’s Sutent (sunitinib), which prolongs the (poor quality) life of sufferers from kidney cancer by on average six months at a cost of £74 a day. NICE, the cost-effectiveness medical traffic cop, originally blocked its use by the NHS, then reversed itself. (Of course, in the USA insurance companies routinely waive petty red tape that might bar such treatments for the insured, and hospitals offer them for the uninsured pro bono. Oh, wait…)

Is there any good way of looking specifically for cures? Very doubtful. At first sight, you just have to throw money at understanding disease, hoping that you will eventually get cures as well as treatments. Note that Big Pharma research is biased towards treatments. Up to around 1970, as I understand they basically screened chemicals randomly for activity. Now it’s all based on knowledge about genes, pathways and receptors: so the researchers focus on rich-country diseases and incremental improvements on stuff they understand, and ignore malaria and long shots. You would have to be paranoid to think they are actually suppressing silver bullets, but they don’t have much of an incentive to look for them.

We should stand by Thomas’ hope. Hope it is, in the strong, theological sense: a vision of a different world that inspires action towards it. A world in which you are diagnosed with an incipient cancer, hooked up to the autodoc for a day and it’s gone. A world in which medical costs don’t threaten the prosperity of nations and crowd out other urgent public goods.

A pipe dream? Ask Edward Jenner, Alexander Fleming, Jonas Salk, Albert Sabin, Jimmy Carter, Barry Marshall, and Gero Hütter. And those whose lives they have changed.

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