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Profits cost us cures

I know nobody here needs convincing that the free market doesn’t provide the best medical care for all. But it’s not just the care part that struggles. The real heart of medicine is cures and, best of all, preventing disease altogether. Profit-driven drug delivery actually hampers finding the best solutions.

I’d say the most insidious effect is how research gets shunted away from the really good stuff. That takes away benefits in the future, and we don’t even know what we’re missing. It could be the cure for cancer or a vaccine against the common cold. Maybe it’s something that makes childbirth feel like orgasm. (Contractions are contractions. It’s an interesting question why there’s such a big difference in felt sensations.) The point is we don’t even know.

And don’t even get me started on what’s painfully obvious: the fact that prevention can never be a priority in a profit-driven system. Prevention can never be expensive because the customers aren’t desperate. It’s that simple. And because it has to be cheap, the profit margins can never be large. Besides, if it totally works–one vaccination or one pill and you’re done–there isn’t even any repeat business. Benefit to the consumer: priceless. Benefit to the drug company: pennies. Result: prevention is boring.

There are solutions, no question about that, but they can’t come from the “market.” They’re the same as for any endeavor with huge social benefits that doesn’t pay off for any single individual: regulation and government action. That doesn’t always have to be expensive. Imagine, among many other necessary changes, a law which applied to federally funded scientists, i.e. practically all of them. If they had useful prevention-related results (not just “research”), they had to be given priority in hiring. That would focus people’s minds.

Okay. Back to the new technologies we’re missing because the opportunities for profit aren’t too good. There’s a common thread that runs through several of them.

One of the dominant themes in biology is infinite diversity in infinite combination. (You thought they just made the Vulcans up, didn’t you?) That means that the most effective cures are tailored to specific patients, specific bacteria, specific tumors, to a very narrowly focused situation.

There’s not a lot of money in narrowly focused situations. If you’re Merck, you want to sell your drug to millions, better yet billions, not just fifteen people in Poughkeepsie. And, in fairness, it has to be said that the process for getting regulatory approval for a drug takes around seven years and hundreds of millions of dollars. Unless there’s some way to spread that cost around, you can’t even blame companies for not working hard at drugs that serve a small number of people.

Consider phages, a treatment that’s not all that new, that’s never gone much of anywhere because it’s individualized. Say what? you’re probably thinking. Never heard of ’em. They’ve been around as a treatment for bacterial diseases since the 1930s, before penicillin. Phages is short for bacteriophages, which are viruses that attack bacteria. Of course, this being biology, specific viruses attack specific bacteria.

So, in order to find a phage treatment for strep throat, for instance, you have to find the specific bacteriophages that attack the strains of bacteria causing the disease. No silver bullets here. But when you do find the right bullet, it wipes out the disease with zero side effects of any kind. And there is no way for bacteria to develop overall resistance, because phages evolve even faster than they do.

Given the rapidly increasing problem of antibiotic resistance, and the potentially catastrophic outcomes if it gets out of hand, why aren’t the drug companies doing more with this?

There are two real problems with phages. Viruses can’t necessarily get to all the places where the bacteria are (and vice versa). No phages are known so far for the bacteria that cause some serious diseases (leprosy, tuberculosis, botulism).

But other than that, all the problems fall into the “stupid” category. Drug companies would have to maintain libraries of thousands of different phages. Any one phage would only be used rarely. They’d continuously have to be screening for new phages. Phages and bacteria evolve a lot faster than the regulatory process, and light years faster than the patent process. There’s no easy way to “own” them. The approval process is stuck in the Dark Ages. Meanwhile, drug resistance marches on and the drug companies concentrate on important drugs, like Alli, that can help people lose a whole extra three pounds a year and rake in millions.

A much newer development is in the field of tailoring drugs to specific individuals. One of medicine’s least-publicized aspects is that drugs work differently in different people. It was expressed clearly in a BBC report (Dec 8, 2003).

Drugs ‘don’t work on many people’
A senior executive at Europe’s largest drug maker has admitted most prescription medicines don’t work for most people, it is reported.
Allen Roses, of GlaxoSmithKline, is quoted in a national newspaper as saying more than 90% of drugs only work in 30-50% of people.
He said: “Drugs on the market work, but they don’t work in everybody.”
Mr Roses, an expert in genetics, said new developments should help tailor drugs more specifically.
At present, pharmaceutical companies adopt a “one-drug-fits-all” policy.

At the time, the type of genome testing which would take the guesswork out of matching drugs to individuals was still hugely expensive. The costs are coming down, but there’s no excitement in the pharmaceutical industry about making sure every individual gets the most suitable drug. They’re hardly doing the obvious stuff that doesn’t take any testing, like making sure drugs shown to be most effective in a given gender or ethnic group are prescribed accordingly. What would be the incentive to shrink your market? Especially if a competitor’s product is better for a given person?

In Europe, with their better-developed social consciousness, there’s talk of getting the companies to work on it. The BBC again: “[There are] calls for financial incentives to be introduced to encourage research in the UK and Europe and to encourage pharmaceutical companies to work on developing pharmacogenetic drugs which are likely to have relatively small potential markets. ‘If medicines were able to target an individual patient’s cancer, they would work more effectively’ [said] Professor John Toy, Cancer Research UK.” (They better make sure the companies don’t treat the incentives in their usual all-contributions-gratefully-accepted manner.)

An added wrinkle is that in cases of cancer, tumors with different genetic profiles have different susceptibilities to chemotherapy drugs. It becomes a matter of life or death to find the most effective combinations. In these cases, grudgingly it seems, drug companies actually try to figure out and promote the correct match, such as in the cases of Herceptin-susceptible breast cancer tumors.

Even more individualized is the treatment of tumors with monoclonal antibodies. Remember the complement proteins that could bind with specific proteins on the surfaces of cancer cells? (Discussed in Ten Minute Cancer Test. You can attach many different things to those complement proteins, like antibodies that mark the cell for destruction by the immune system. They bind to their match on the cancer cell, and wave a flag around saying, “Come kill this thing.”

The “antibody” part is the flag. The “monoclonal” part is how they’re made. Cliff Notes version: a sample of the patient’s own specific type of white blood cell is taken (B-cell), and exposed to the unusual proteins on the tumor. Once the B-cells start producing an antibody targeting a specific tumor protein, that line of cells is grown in quantity. Once there are loads of antibody-producing cells, they’re injected back into the patient and all attack the tumor. Unfortunately, tumors are good at evolving to evade the immune system, so monoclonal antibodies often provide remission rather than cure. However, recently it’s been discovered that the tumor cells’ ability to evade can be crippled with another drug, and then they’re really helpless. Early results indicate tumors tend to melt away.

Everything about the process is individualized, both the tumor genetics and the need to culture the patient’s own white blood cells for the procedure to work. All the difficulties of getting the industry to work on small-market drugs are compounded. These aren’t just small markets. These are one-person markets. Knowledge about using monoclonal antibodies in medicine has been around for a few years, but there’s been no rush to make kits hospitals could use for individual patients. People keep doing research.

(I should mention that the results of monoclonals aren’t always nice. There was a horrific miscarriage of a medical trial on six volunteers in England who were testing a neurological monoclonal antibody treatment for safety. Turned out something wasn’t at all safe. They had massive systemic immune reactions, two of them nearly died and have permanent damage. There are questions about how the drug was administered, and whether the antibodies themselves were at fault, but it’s still not clear what caused the tragedy.)

Equally individual are stem cell cures that use the patient’s own stem cells. Those are the only kind that avoid the need for lifelong immunosuppression, since there’s a brouhaha about using embryonic stem cells. So the only usable cells are specific to a given patient … but the pharmaceutical industry does its best to ignore one-off treatments.

Research has shown good results using stem cells to regenerate insulin-producing cells to treat juvenile (Type 1) diabetes, dopamine-producing cells to treat Parkinsons, and retinal cells to treat macular degeneration. How soon will it get beyond research? Who knows.

There’s another low tech and longstanding issue affected by the profit motive. Unlike prevention, where the customers won’t pay, diseases of poverty are boring because the customers can’t pay. Result: hundreds of millions of people suffering and dying from preventable diseases. And in these days of air travel, the notoriously cavalier attitude of diseases to borders means the people suffering won’t necessarily be “over there” somewhere. (E.g. as I write, this appeared: WHO warns of global epidemic risk.)

Diseases also cripple whole economies. The economic refugees then flood other countries. That creates more than humanitarian disasters, assuming that some people see those as cheap. It also costs lots of money in industrial countries that have to seal borders, deal with social unrest, worry about violence, and have wages depressed throughout their own economies. So even though pharmaceutical companies can’t make things like malaria cures pay enough, it would be priceless for hundreds of millions of human beings, and industrial countries would also benefit enormously. But the profit motive can’t make it happen.

Finally, just to round out this dismal saga, the regulatory process and legal system also have to take some of the blame. Take the example of the monoclonal antibodies, which work best when used with another drug. Neither by itself really does the job. Together they do an amazing job. But the approval process is for one drug at a time, and each drug in isolation is “not effective.” Ineffective drugs can’t get approval.

Is that braindead, or what?

Or take the example of vaccines. They take lots of research and testing, which is expensive, and all that for a preventive medicine which can’t cost much. But then, just to keep things interesting, along come lawyers threatening suits about anything they hope a medically uneducated jury will believe. Vaccines have been turned into such a black hole of testing costs and legal expenditures that at this point there’s only a handful of companies who will have anything to do with them. The loss to society is immense. Just how immense will become painfully obvious the first time we don’t have enough vaccines to go around during an epidemic. (We’ve had some minor events already. Believe me. Those were very minor.)

I’m not saying vaccines shouldn’t be safe. Of course they should be. But it’s also true that the law is not effective at keeping up with science on this. How it should be changed, I don’t know, but that it should be changed is self-evident.

I could go on about this forever. (What? You noticed?) What I’d really like to see is people understanding the deeper problem with our health care crisis. You can’t always get what you want, so you have to decide what you need. And this is true at every level, not just insurance. Research, drugs, prevention, and care, all suffer from woolly priorities about health versus money. The national health insurance debate needs to be expanded to include that central problem.

If we decide we want health rather than money, we have to get our heads around the concept that we have to pay for it. Saving lives is never a moneymaker. If we decide we want money rather than health, we have to be prepared to let people die in the street.