In these difficult economic times, it is not surprising that many people are scavenging the basement for goods to sell on E-bay. Most people don’t realize that there are valuable (and renewable) personal possessions available for sale closer to hand: their own cells.

A market for blood components, such as plasma, has long existed because the need is so high. Recently, however, new cellular products have become far more lucrative. These are sperm, and, especially, eggs (ova).  An article on MSNBC highlights the rise in inquiries about paid donation:

…Seeking quick cash in a tanking financial market, would-be sellers of a variety of body products — sperm, eggs, blood plasma, even human hair — are filling waiting rooms and swamping agencies with inquiries.

Increasingly, industry officials say people are hoping to trade spare body fluids, tissues and other parts for payments that can range from $20 to $50 a pop for blood plasma to $60 to $100 for a shot of sperm, $200 for a shiny ponytail and up to $7,000 for a fertile egg.

At the Seattle Sperm Bank alone, donor applications have tripled from 50 to 150 a month during this financially precarious autumn, staff members said, while officials at egg donation agencies from Chicago to Houston estimate that calls are up at least 30 percent over last year.

Organizations that pay for donations insist that donors aren’t motivated by money, or at least not motivated solely by money:

…Christine Kuhinka, a spokeswoman for ZLB Plasma, which operates 66 centers across the country, said she believes more donors are being motivated by altruism.

“There are many reasons to donate plasma,” she said. “At the end of the day, most people recognize that they’re saving lives.”

But blood industry experts said it’s disingenuous to claim that compensated plasma isn’t tied to a faltering economy.

“I am confident that paid plasma increases in tough economic times as a direct result of the economy, and would love to see the data used by plasma companies that says it is not,” said Dr. Louis M. Katz, executive vice president of the Mississippi Valley Regional Blood Center in Davenport, Iowa.

The opportunity to donate plasma, sperm and eggs in exchange for financial compensation highlights an ethical paradox in US healthcare. While sale of cells for money is allowed, sale of organs is strictly prohibited. According to Payment for donor kidneys: Pros and cons by Friedman and Friedman:

…The National Organ Transplant Act states: ‘It shall be unlawful for any person to knowingly acquire, receive, or otherwise transfer any human organ for valuable consideration for use in human transplantation if the transfer affects interstate commerce.’ Punishment includes fines up to $50,000 and/or 5 years in prison, but has not been meted out. A year after enactment of National Organ Transplant Act, the Ethics Committee of the Transplantation Society issued a supporting Policy Statement: ‘No transplant surgeon/team shall be involved directly or indirectly in the buying or selling of organs/tissues or in any transplant activity aimed at commercial gain to himself/herself or an associated hospital or institute.’

A variety of ethical principles are invoked to justify this ban, even though it may inadvertently sentence to death many people in need of replacement organs. Thousands die each year for lack of people who donate for altruistic reasons during life or after death. Opponents of paid organ donation argue that compensating people for their own organs violates the principle, articulated by the philosopher Immanuel Kant, of intrinsic human dignity. More prosaically, opponents point out that the need to donate for cash will not fall equally on all members of society. The poor and the socially marginized will be under much greater pressure to donate for financial reasons than other members of society.

Other countries do not share the illogical combination of policies favored by the United States. Canada bans financial compensation for all donations, organs and cells. At the opposite end of the spectrum, many countries pay only lip service to legal bans on organ donation. India, China and Russia, among others, have thriving trades in replacement organs.

In the US, we are even inconsistent about our inconsistency. While donation of eggs (ova) for use by infertile couples is generously compensated, donation of eggs for stem cell research is typically not compensated at all. Partly this is the result of the controversial nature of stem cell research under the Bush administration. However, it also reflects our ambivalence about the various uses of donor cells. The creation of human embryos to treat infertility is viewed very differently than the creation of human embryos for use in research.

Can selling cells be ethically justified within a system that bans selling of organs? Without financial compensation, the supply of donor sperm will drop precipitously, and the supply of donor eggs will likely disappear altogether. Yet that is hardly as disastrous an outcome and the thousands of deaths resulting from a ban on selling organs.

Art Caplan, director of the Center for Bioethics at the University of Pennsylvania, knows where he stands:

“The uptick [in donation for money] gives lie to the system that invokes ‘donors’ when it’s really a system of ‘sellers,’”…

“Altruistic motivation isn’t going up,” he added. “The drive to get paid is going up.”

Caplan worries most about donation of genetic material such as sperm and eggs. People who need cash may not be truthful about their medical background, for instance. Or they might be so desperate for money, they don’t think through the potential for physical and emotional complications.

“In economic hard times, if somebody went out to sell a baby, there would be moral contempt,” he said. “But if you sell the ingredients for a baby — and the oven — we don’t pay attention.”

There was a scandal in my small town several years ago when a respected couple was arrested for hosting an alcohol soaked party for middle school students at their home. I don’t remember the details, but I do remember the parents’ defense. They claimed that young teens were going to use alcohol anyway; therefore, it was better if parents provided it and supervised its use.

I was reminded of that case by a controversial commentary, Toward responsible use of cognitive-enhancing drugs by the healthy, published yesterday in the scientific journal Nature. The opinion piece is sure to provoke a firestorm of protest. The authors argue that everyone, healthy people included, should have easy access to cognition-enhancing drugs like Ritalin because, in the words of author Martha J. Farah, “Almost everybody is going to want to use it.” Indeed, the use of Ritalin and other stimulants by healthy college students ranges from 4% to as high as 25% on some campuses. According to Farah, “It’s a felony, but it’s being done.”

This piece makes no sense to me. The authors publish a call for universal access to brain stimulants in the absence of sound scientific research, in the absence of evidence that this is a problem worthy of societal attention, and based on an inane defense that it should be allowed because people are going to use them illegally any way. As Leigh Turner of the University of Minnesota Center for Bioethics said, when asked to evaluate the commentary: “It’s a nice puff piece for selling medications for people who don’t have an illness of any kind,” Turner said.

What does the piece say?

Today, on university campuses around the world, students are striking deals to buy and sell prescription drugs such as Adderall and Ritalin — not to get high, but to get higher grades, to provide an edge over their fellow students or to increase in some measurable way their capacity for learning. These transactions are crimes in the United States, punishable by prison…

 In this article, we propose actions that will help society accept the benefits of enhancement, given appropriate research and evolved regulation. Prescription drugs are regulated as such not for their enhancing properties but primarily for considerations of safety and potential abuse. Still, cognitive enhancement has much to offer individuals and society, and a proper societal response will involve making enhancements available while managing their risks.

In the opening paragraphs, the authors make several bizarre claims. In addition to the claim that everyone is doing it, the authors insist that cognitive enhancement offers many benefits, and that the only role of regulation is safety. Therefore, we, as a society, should figure out how to provide these “benefits” in a safe manner, while presumably decriminalizing the trade of these drugs by individuals.

Drugs like Ritalin have been used successfully to treat attention deficit disorder with and without hyperactivity (ADD/ADHD). There are also reports of therapeutic benefits in cognition in patients with brain tumors, strokes and traumatic brain injuries. However, when it comes to the use of stimulants among healthy young adults, there is surprisingly little scientific information available.

In discussing safety, the authors mention three issues, long term risks, pressure to self medicate, and fairness, but, surprisingly fail to discuss the most important issue, the fact that stimulants like Ritalin are drugs of abuse. We do not have a clear idea of the long term effects of using Ritalin. The information we have at present suggest that stimulants can be safe for long term use in therapeutic settings, allowing us to balance the known benefits of stimulants in therapeutic settings against the unknown, though probably small risks.

There is no reason to assume that the same calculus applies to using stimulants in healthy individuals. Consider a different class of drugs that may offer a useful parallel, opiates. Opiates are extremely beneficial in a therapeutic setting, and although they have both short and long term risks, those risks are usually justified by the benefits. When opiates are used in non-therapeutic situations, to create a “high,” the benefit risk calculus is very different. The “benefit” is not necessarily beneficial, and the long term risk of addiction is far greater. Stimulants, like opiates, are known to be drugs of abuse and addiction even in therapeutic settings. It is quite possible that they are more likely to lead to abuse and addiction when used by healthy people.

The authors devote far more attention to ethical issues of fairness than to the currently more pressing issues of benefits and risk. Their answers to their own ethical questions are hardly better than the inadequate answers to the empirical issue of safety.

Addressing the issue of the morality of using cognitive-enhancing drugs, the authors say:

Human ingenuity has given us means of enhancing our brains through inventions such as written language, printing and the Internet…The drugs just reviewed, along with newer technologies such as brain stimulation and prosthetic brain chips, should be viewed in the same general category as education, good health habits, and information technology — ways that our uniquely innovative species tries to improve itself.

Are these people serious? Brain stimulation and prosthetic brain chips should be viewed in the same category as education? That is a claim that begs for ethical justification and the authors don’t bother to provide any. Blithely assuming that their claim is self-evident, they proceed to two other ethical concerns.

The authors clearly assume that stimulants for cognitition-enhancement in healthy people can and will be widely available. However, they are concerned that when that great day comes, some people will be left out, either because they don’t wish to self-medicate or because they can’t pay for the drugs.

Those concerns are, not surprisingly, similar to issues raised by performance enhancing drugs in sports. If everyone is using steroids, what happens to those who refuse to self-medicate with steroids or can’t afford steroids? Interestingly, we, as a society, have not chosen to make steroid use legal in athletics, nor are we insisting that athletes must use steroids, and we are not offering free steroids to promising high school athletic stars. Nonetheless, this is the direction that the authors of the commentary are pushing us toward in regard to stimulant use.

Who wrote this commentary, and how did it get published in the prestigious and highly respected journal Nature? Of the seven authors, two are consultants for drug companies and one is an editor of Nature. The other four claim to have no conflicts of interest. However, it is a matter of public record that some of their affiliated institutions have financial relationships with drug companies.

At a minimum, it is distressing that Nature has published an article where three of the authors have a clear conflict of interest, including one of their own editors. I want to emphasize that I have no information that the other four authors have any financial ties to the pharmaceutical industry. However, in light of multiple scandals in which authors of papers in both The New England Journal of Medicine and The Journal of the American Medical Association (JAMA) were subsequently revealed to have concealed financial ties to industry, I can only hope that the editors of Nature did more than simply take the authors’ word on potential conflicts of interest.

This commentary is inexplicable. There is no good science to back up its assertions; it ignores the principle risk of drug abuse; and it encourages us to take action on an issue that should be very far down our agenda. And like the parents who were arrested for providing alcohol to minors, its principle justification is that everyone is going to do it anyway. That’s not even a remotely reasonable defense for providing alcohol to minors, and it is not a remotely reasonable defense for providing cognitive-enhancing stimulants to healthy people

Imagine finding that in your e-mail in box. If sex educator Deb Levine, and Dr. Jeffrey D. Klausner have their way, that will be increasingly likely to happen. Levine and Klausner have created an innovative campaign to make it easier to find the partners of people with sexually transmitted diseases. Levine, Klausner and colleagues have recently published a scientific paper detailing their experience with e-mail notification for sexually transmitted diseases (STDs).

Mandated state reporting of STDs has existed for decades. Mandated reporting was instituted because STDs are easily transmitted, often produce no symptoms in those who are infected, and can cause long term health problems when undiagnosed. The mandated reporting puts the state in charge of making sure that partners are notified and come in for treatment. Doctors are required to report all cases of certain STDs that they diagnose.

The e-mail innovation is a response to rising rates of casual sex, when partners may know nothing more than a first name and e-mail address of a sexual contact. According to MSNBC:

The service is the creation of Deb Levine, a sex educator and author of a book called The Joy of Cybersex, and of Dr. Jeffrey D. Klausner, director of STD Prevention and Control Services for the San Francisco Department of Public Health.

“In 2001 I noticed a big rise in the number of syphilis cases among gay men,” recalls Klausner. “In 1998 it was about five cases. By 2001 we had 150 cases.”

Klausner set out to discover why the rate jumped and learned that men had begun meeting each other online for casual encounters. Those encounters may be anonymous, but usually involve an exchange of e-mails. “That turned on a light for me and I realized we needed to do something online.”

He tracked down Levine … and the two created ISIS, a non-profit community organization to put sexual health information online. One of their first projects was the e-mail notification system.

The service is called inSPOT:

More than 750 people visit the inSPOT site daily. Since 2004, the service has sent more than 49,500 e-cards. Syphilis and gonorrhea cases have each accounted for approximately 15 percent of the total cards sent, followed by chlamydia at 11.6 percent and HIV at 9.3 percent. More than half a dozen other diseases account for the rest, including crabs and scabies; hepatitis A, B and C and trichomoniasis, a parasitic STD.

How does it work? In October, the online journal PLOS Medicine published the paper inSPOT: The First Online Partner Notification System Using Electronic Postcards, detailing the system and the results.

On the rationale for the system:

In the United States there are 19 million new sexually transmitted disease (STD) cases diagnosed each year, including 900,000 reported cases of chlamydia, 330,000 reported cases of gonorrhea, and 55,400 estimated new HIV infections per year. Notifying sexual partners of their potential exposure to an STD has been a mainstay of disease prevention and control since the 1930s…

Traditionally, partner notification has been done in person, by phone, or by mail, with the assistance of a public health investigator. The high number of cases … makes partner notification for all named partners impractical in many jurisdictions. Particularly among gay men and other men who have sex with men (G/MSM), who tend to have higher numbers of partners, online notification may be an effective strategy to increase partner notification.

E-mail notification is sent by the infected person, because he or she often has nothing other than an e-mail address to identify the partner, and therefore cannot identify the partner for state reporting efforts:

… inSPOT is very simple. The two sections are Tell Them and Get Checked. In Tell Them, users follow this path:

·         Choose one of six e-cards,

·         Type in recipients’ e-mail addresses (up to six),

·         Select an STD from a pull-down menu,

·         Type in own e-mail address or send anonymously,

·         Type in an optional personal message.

When an e-card is clicked on by the recipient, users are linked to a page with disease-specific information.

The Get Checked section is divided into STD information, a map of local testing sites, and links to online resources. To ensure the privacy of the user, no database to store e-mail addresses or information about e-card senders or recipients exists.

Since its 2004 launch in San Francisco, inSPOT has been replicated in three countries, ten cities, and nine states…

How well does inSPOT work? The authors are extremely enthusiastic, but, in truth, the results are quite modest:

…[W]e analyzed rates at which e-card recipients clicked a link embedded in the card that connected to STD test site information. Annual “click-through” rates ranged from 20.4% in Los Angeles to 48.2% in Idaho, with an average across all sites of 26.8% in 2006 and 28.5% in 2007. During the period that inSPOT has been active, from December 2005 through February 2008, 29,137 people accessed STD testing information as a result of receiving an e-card…

Only one quarter to one half of recipients clicked through to the information about getting tested for the disease to which they were exposed. There is no information about what proportion actually got tested. Accessing the information does not mean that the recipient got tested, and not clicking through to the information does not preclude the possibility that the recipient sought testing through a private doctor. However, when you consider that none of the recipients could have been notified any other way, even small testing rates are encouraging.

The inSPOT notification system is a high tech response to a distinctly high tech modern problem. The internet has created an unprecedented opportunity for soliciting casual sexual encounters. This has contributed to an increase in sexually transmitted diseases, and an increasingly inability to identify sexual contacts of an infected person. It is fitting that the technology used to fuel the increase is also being used to limit its negative impact.

Some think that the inSPOT e-mails are already outmoded. E-mail is increasingly a tool of older people; teens and young adults have moved on to text messaging. According to Mary McFarlane, a behavioral scientist with the Division of STD Prevention at the Centers for Disease Control and Prevention in Atlanta:

“More and more people are going with mobile phone technology” to facilitate casual hookups she says. “I think it is very important that we in public health pay attention to these innovations and provide health information in those places.”

No doubt a text messaging service is on its way. In the near future, people may retrieve their text messages to find:

Wlcm! Yv gt syphilis!

 

 A paper by Dr. Mark Heaney and colleagues published in the October issue of Cancer Research revealed a startling finding. When leukemia and lymphoma cells were exposed in the lab to dehydroascorbic acid, they were less likely to be killed by chemotherapy. Cells that had been exposed to dehydroascorbic acid were better able to survive treatment with doxorubicin, cisplatin, vincristine,methotrexate, or imatinib, five widely prescribed chemotherapy agents that act in a number of different ways.

Why should the average person care about this study? This study provides a valuable warning to cancer patients because dehydroascorbic acid is vitamin C.

In interviews, the authors were careful to point out that this is lab research taking place in petri dishes, not clinical research done in humans. However, the findings are disturbing in light of the fact that many cancer patients take vitamin C supplements. Rather than boosting the immune system, vitamin C supplements may actually boost the cancer cells.

As recently as August of this year, alternative health practitioners like Joseph Mercola, were touting high dose vitamin C supplements as highly effective against cancer. At this moment, many alternative health websites still recommend vitamin C supplements as “treatment” against cancer. The “theory” is that vitamin C, an antioxidant, interferes with the action of free radicals, chemicals known to damage cells. Supposedly, since damage to cells causes cancer, and since antioxidants prevent damage to cells, antioxidants “treat” cancer.

The irony is that vitamin C appears to act in precisely the opposite way. Yes, vitamin C is an antioxidant that reduces cellular damage from free radicals, but some chemotherapeutic agents are free radicals that kill cancer by damaging the individual cancer cells. Vitamin C supplements appear to inactivate chemotherapy, either by inactivating the drugs themselves or by interfering with the action of the drugs. Indeed, the authors found that vitamin C reduced the cancer killing ability of chemotherapy by 30-70%, depending on the chemotherapy drug.

What did the authors do in the study? The authors exposed leukemia and lymphoma cells to dehydroascorbic acid, the form of vitamin C that appears in the blood stream after taking supplements. Then they compared the effects of chemotherapy on those cells with sister cells that had not been exposed to vitamin C. They did this in two ways; first by exposing cells to chemotherapy drugs, and second by transplanting cells into mice, generating tumors, and then treating the mice with chemotherapy. In both cases, in the petri dishes and in the mice afflicted with cancer, exposure to vitamin C dramatically reduced the ability of the chemotherapy drugs to kill the cancer cells.

These findings are in keeping with a large number of studies that have shown that vitamin C can neither prevent nor treat cancer, most importantly a recently released, large scale study of vitamin C use among 14,600 male doctors participating in the Physicians Heart Study II. Participants received either vitamin C or vitamin E supplements or placebo for 10 years. The study was undertaken to look at the effects of vitamin supplements on heart disease, but the authors kept careful records of all other medical outcomes in these groups. The principle finding of the study was that vitamin C and vitamin E supplements had no effect on the risk of heart attack or stroke. A secondary finding was that vitamin C (and vitamin E) had no effect on cancer risk, either.

While cautious about the preliminary nature of the study, Dr. Heaney, the scientist who tested vitamin C on leukemia and lymphoma cells, expressed his concerns in an interview with Medscape Oncology:

“Our study is a preclinical model that addresses only the situation when vitamin C is given in the setting of chemotherapy treatment,” Dr. Heaney emphasized. There have been no clinical studies of this topic so far, he said.

However, the finding could be of potential concern because “many people, cancer patients included, take supplemental vitamin C,” Dr. Heaney pointed out. Clinical studies of vitamin C supplementation in patients with advanced cancers have had mixed results. There are conflicting hypotheses, he explained. One theory is that vitamin C supplementation protects the cancer and is therefore detrimental to the patient…

Medscape Oncology interviewed another doctor with no connection to the study:

Asked to comment on this study, Len Lichtenfeld, MACP, deputy chief medical officer at the American Cancer Society said: “Vitamin C has a long history in cancer prevention and treatment. Although there is no evidence to demonstrate that vitamin C improves the outlook for patients with cancer, there are still reported observations that cancer patients continue to believe in the potential benefits of vitamin C. Although oncologists do not routinely recommend that patients with cancer take excessive doses of vitamin C, there are reports that cancer patients are being treated with vitamin C by alternative practitioners…”

… [T]he current report suggests that in laboratory experiments, adding vitamin C to cancer cells may reduce the effectiveness of cancer chemotherapy drugs.

“Clearly, there remains an open question as to whether or not vitamin C supplementation is helpful or harmful in the treatment of patients with cancer. Until those questions are resolved with further clinical studies, it would be inappropriate to recommend that patients take large quantities of vitamin C if they have cancer,”

Many cancer patients explore alternative treatments like vitamin supplementation, reasoning that while they may not be help, they are not likely to be harmful. This study demonstrates that such assumptions may be totally false. Supplements like vitamins and herbs have chemical actions of their own, and those chemical actions may interfere with the effectiveness of conventional treatment, or inadvertently improve the survival ability of the cancer, not the patient.

The most important message to take away from this study is that no one should take alternative treatments of any kind without discussing them with their doctor, to be sure that there are no harmful interactions. It would be tragically ironic if cancer patients were actually supplementing their cancer, instead of fortifying themselves for the fight against the disease.

 The British government has been trying to answer that question, or rather, a variant: How much should they pay for 6 more months of your life? By explicitly framing the question, let alone answering it, the government has put itself at the nexus of 4 ongoing controversies in medicine: Should medical care be rationed? How much is longer life worth? Does evidence based medicine accurately give us the answer? Should governments deal with drug companies that price drugs without reference to their actual cost?

The United Kingdom came down on the side of rationing healthcare years ago. They were honest enough with themselves, and the people of their countries, to acknowledge that there was not enough money to support unrestricted healthcare for all. Forced to choose between providing unlimited healthcare for some vs. limited healthcare for all, those chose healthcare for all. Both the government and the people understood that the annual healthcare budget was finite, that paying for expensive treatments would reduce money available to meet the needs of everyone else, and that a transparent, rational method must be found to make the necessary decisions. Everyone agreed in theory; in practice there has often been tremendous public outcry.

In an effort to create a transparent, rational basis for limiting care, the British government formed the National Institute for Health and Clinical Excellence (NICE). NICE evaluates all forms of medical care through a very extensive review process, solicitng the opinions of all possible stakeholders in every decision. NICE routinely produces voluminous reports reviewing the scientific literature and issuing guidelines for virtually every aspect of care. For example, the NICE guideline for the care of healthy women during childbirth (excluding pregnancy, excluding high risk women) runs to 332 pages and includes review of 628 separate scientific studies.

Almost every decision of NICE carries some element of controversy, but none more than decisions about expensive treatments that lengthen life but do not cure the terminally ill, the elderly, or those unfortunate enough to have rare diseases. NICE is explicit about the criteria. According to an article in The New York Times:

… Any drug that provides an extra six months of good-quality life for £10,000 — about $15,150 — or less is automatically approved, while those that give six months for $22,750 or less might get approved. More expensive medicines have been approved only rarely. The spending limits represent the health institute’s best guess for how much the nation can afford.

Not surprisingly, many state of the art medications exceed that price. The newest treatments for diseases as diverse as multiple sclerosis, advanced renal (kidney) cancer, and Alzheimer’s disease are not covered. The public outcry has been fierce.

No one disagrees with the fundamental principle of rationing healthcare. No one is challenging the evidenced based claims that the drugs provide only limited extension of life for extraordinary cost. The decisions are acknowledged to be both moral and rational based on the agreed upon criteria. They are challenging the decisions as “heartless.”

Bruce Hardy, interviewed for the New York Times article, is an example:

When Bruce Hardy’s kidney cancer spread to his lung, his doctor recommended an expensive new pill from Pfizer. But Mr. Hardy is British, and the British health authorities refused to buy the medicine. His wife has been distraught.

“Everybody should be allowed to have as much life as they can,” Joy Hardy said in the couple’s modest home outside London.

…A clinical trial showed that the pill, called Sutent, delays cancer progression for six months at an estimated treatment cost of $54,000.

Initially, NICE held firm on its decision to refuse payment, even though only a relatively small number of people need the drug.

Given that fewer than 6,000 people per year in England and Wales are diagnosed with kidney cancer, “Why put ourselves through so much heartache for very little money?” Andrew Dillon, the institute’s chief executive, asked in a September interview. “The answer is that if we don’t apply the same criteria even to small groups of patients, there’s little value to what we do at all.”

In the face of increasing political pressure, NICE has recently backed down. Guess who was among the first to report the turn around: the Pharmaceutical Business Review.

The National Institute for Health and Clinical Excellence in the UK may lift the ban on certain kidney cancer drugs reversing its earlier decision to ban four drugs on the NHS – Sutent, Nexavar, Avastin and Torisel.

Previously, the National Institute for Health and Clinical Excellence (NICE) has refused to approve the kidney cancer drugs as they cost more than $70,000 a year per patient. However, the public outcry against its decision and availability of new data regarding the effectiveness of the drugs has forced NICE to overhaul its previous decision…

Pfizer and Roche, the makers of Sutent and Avastin, are also believed to be in talks with NICE regarding a new a pricing arrangement that would see the NHS paying for a drug if it extended a patient’s life by an agreed time. However, if the patient experienced no benefit and died, the pharmaceutical company would refund the cost.

The decision of NICE to pay for the drugs is a victory for the patients. However, it is also a financial bonanza for the manufacturers. It is a bonanza that many believe the drug companies do not deserve, because it is their extortionist pricing policies that led to the problem in the first place. The Times article offers a shocking example:

…Take the case of Celgene, the maker of Revlimid, a drug for multiple myeloma, a bone-marrow cancer, that in a preliminary ruling on Oct. 28 the institute said was too costly.

Celgene’s first big seller was thalidomide, a decades-old medicine now used as a cancer treatment, which is so cheap to manufacture that a company in Brazil sells it for pennies a pill.

Celgene initially spent very little on research and priced each pill in 1998 at $6. As the drug’s popularity against cancer grew, the company raised the price 30-fold to about $180 per pill, or $66,000 per year. The price increases reflected the medicine’s value, company executives said.

In 2005, the company introduced Revlimid, a derivative of thalidomide that is supposed to be less toxic, but may be no more effective. Celgene priced it at about $260 per pill, or $94,000 per year.

The drug company, Celgene, was already making a large profit when it marketed the treatment at $2,2000 per year. Then it arbitrarily chose to increase the cost of the treatment to $66,000 per year, at the highest price it thought the market would bear. Who was willing to pay for such a massive and arbitrary price increase? The government of the US was willing to pay, because George W. Bush and cronies had forced through an addition to the Medicare bill of 2007 explicitly barring price negotiations with drug companies. Bush made it clear to the drug companies that the US government would pay the highest price that the company could dream up.

These irresponsible give-aways have put tremendous pressure on everyone else. Drugs are deliberately and exorbitantly overpriced for the US market, making them unaffordable for countries whose goal is to provide healthcare, not to line the pockets of drug company executives. The unwillingness of the British government to pay, backed by the evidence based reports of NICE, has led drug companies to negotiate with the British National Health Service.

Though political pressure forced NICE to back down on its refusal to pay for Sutent and similar drugs, it did not back down completely. It negotiated a performance based pricing structure for the drugs. If the medication does not provide the promised benefit, the British government will not have to pay.

What are the lessons for the US? First and foremost, as the largest purchaser of drugs in the US, if not the world, the US government must be liberated from its absurd inability to negotiate with drug companies. That will go a long way to making treatments more affordable, and therefore more available, to everyone. Second, we have no choice but to ultimately follow the British in their attempt to ration and rationalize the provision of healthcare. There is simply not enough money to provide everything to everyone. We may choose to make different decisions and create different cut off points than the British have done, but we will not be able to avoid answering the difficult question: How much should we pay for 6 more months of your life?

One of the thorniest ethical dilemmas in medicine is not who to treat, but how to treat. As new treatments become available for life threatening illnesses, patients and doctors are required to make decisions about whether to stick with the tried and true therapy, and its associated risks and side effects, or switch to the new treatment, which may have fewer risks and side effects, but may be less effective.

Prostate cancer patients already have to make a difficult treatment choice between surgery, radiation and watchful waiting. Surgery and radiation have high cure rates, but both also have high rates of serious complications like impotence and incontinence. That’s because both surgery and radiation inadvertently damage delicate structures like nerves, which are so close by that they cannot be avoided.

A new treatment has recently appeared on the scene, the radiation Cyberknife. Proponents of the radiation Cyberknife claim that it is offers treatment that is far easier (days instead of months) and, because the radiation can be targeted extremely accurately, far less likely to cause serious side effects like impotence and incontinence. Theoretically, it should be just as effective at curing prostate cancer as traditional radiation therapy, but in reality, no one really knows. Hence the ethical dilemma: should the Cyberknife be offered to patients before we have accumulated enough data to be sure that it really works?

I have more than an academic interest in the matter. Eight years ago I chose the Gammaknife for treatment of a benign brain tumor growing within the middle of my brain and pressing on vital structures. Today the Gammaknife is often first line therapy for brain tumors like mine. At the time, though, it was the non-standard alternative, and I might not have even heard of it, let alone chosen it, had I not been a doctor connected with other doctors who were aware of state of the art treatments.

The brain surgeon I consulted strongly recommended surgery even as he counseled that I would lose my hearing on that side and might lose feeling in my face as well. I chose the Gammaknife because the data available at that time suggested that it had an even higher cure rate with a much lower risk of side effects. That turned out to be correct. The new treatment was safer and easier than the old, and was just as effective … fortunately.

Is the Cyberknife a similarly effective alternative to conventional treatment? It has worked very well for tumors of the spinal cord. When it comes to prostate cancer, though, there is far less data available. Indeed, there is less data than the amount of information that was available to me at the time I chose my radiation treatment. Expectations are that, because it is a highly targeted treatment, with the radiation beams “sculpted” to match the exact dimensions of the tumor and spare surrounding tissue, it should be just as effective, and lead to fewer cases of impotence and incontinence. But expectations are just that, expectations, and no one really knows what will happen. Only 2,000 patients have been treated thusfar, and they have been followed for only a few years (not long enough to see long term effects). The preliminary data show that the Cyberknife has a similar cure rate, with fewer short term side effects.

Cyberknife for prostate cancer remains essentially an unproven treatment with great promise. Doctors are struggling with whether it is ethical to introduce such a treatment before it has been proven to be effective. On the other hand, many doctors wonder if it is ethical to withhold such a promising treatment that, theoretically, will reduce the risk of serious and dreaded side effects like impotence and incontinence.

As detailed in a recent Washington Post article, Anthony L. Zietman, president-elect of the American Society for Therapeutic Radiology and Oncology (ASTRO) is opposed to offering the Cyberknife at this point:

“This is really pushing the envelope. It might be as good and more convenient. It may be better and more convenient. But it could turn out to be a disaster. No one knows…”

“We just don’t have the data to support treating prostate cancer with five days of radiation,” said Kevin A. Camphausen of the National Cancer Institute, noting that prostate cancer can recur many years or even decades later. And high-intensity radiation, even though it is more precisely focused, might still damage the rectum, bladder and urethra, potentially causing complications years later.

“What I’m worried about is that we might not be curing patients who we know are curable,” he said.

On the other hand:

Proponents argue that enough evidence has accumulated to make them confident that the approach is at least as good as standard therapies and that it can prevent unnecessary deaths by making treatment less daunting. Because the CyberKnife can more precisely target tumors with higher doses of radiation, it could prove even safer and more effective, they say.

The ethical issues are complicated by the financial incentives. Treating prostate cancer with the Cyberknife represents a tremendous financial boon to the doctors who are advocating its use. They stand to make $1200 per treatment course or more. Cyberknife is faster and more convenient for the doctor as well as the patient. That means that doctors can treat more patients, and make more money, by working the same hours that they worked before. It is not difficult to imagine that this financial advantage could cloud the judgment of Cyberknife proponents.

What does the scientific literature say on this topic? From a discussion of new technologies in radiation therapy:

… While equipment is still developing for the accurate delivery of stereotactic radiosurgery for tumors outside the cranium, many fundamental biological and clinical questions remain regarding the use of these technologies in medical practice…

There is no reason to suppose that all patients or tissue organs will tolerate [treatment] equally well. From the science of radiotherapy, it is understood that toxicities to large radiation fractions are predominantly late occurrences… Since these toxicities may occur late, longer follow-up will be required … [T]here is no reason to suppose that all patients will benefit equally … Only through a consistent and monitored approach will optimal groups be identified for cancer treatment.

In other words, while the new treatment for prostate cancer seems promising, more research is necessary to determine if it is as safe and effective as existing treatments. There is simply not enough scientific research available to guide us. In the meantime, industry is pushing a new and unproven treatment that might be far better than the existing options.

There is only one way to solve this ethical dilemma: the decision must be left to the patient. All options should be presented, and special care should be taken in counseling patients about the unknowns involved in the new treatment. As long as patients realize that they are taking a risk, it is entirely reasonable for them to take that risk in the hope of avoiding serious side effects. This ethical dilemma is similar to many other ethical dilemmas in medicine and the “treatment” is the same: more knowledge and increased patient choice usually represent the best way to move forward.

 

Medicine is a science. Alternative “medicine” is an ideology that is unmoored from science. It usually involves an element of defiance and a belief in conspiracy theories. Proponents of alternative medicine fancy themselves as bravely challenging the unreasoning orthodoxy of medicine. Instead, they have merely allowed their ideology to blind them to the real causes of illness.

When alternative medicine is adopted by a political leader, and the ideology is writ large, thousands of people can die of what amounts to medical neglect. It has already happened. The leader was Thabo Mbeki, the country was South Africa and the ideology was AIDS denialism.

A paper in today’s issue of the Journal of AIDS, Estimating the Lost Benefits of Antiretroviral Use in South Africa, by Chigwedere and colleagues, details the carnage:

South Africa is one of the countries most severely affected by HIV/AIDS. At the peak of the epidemic, the government, going against consensus scientific opinion, argued that HIV was not the cause of AIDS and that antiretroviral (ARV) drugs were not useful for patients and declined to accept freely donated nevirapine and grants from the Global Fund… More than 330,000 lives … were lost because a feasible and timely ARV treatment program was not implemented in South Africa. Thirty-five thousand babies were born with HIV… by not implementing a mother-to-child transmission prophylaxis program using nevirapine. The total lost benefits of ARVs are at least 3.8 million person-years for the period 2000-2005.

Mbeki, the South African president, followed the classic alternative medicine playbook for challenging medicine. According to Paul Wolpe, in The Holistic Heresy: Strategies of Ideological Challenge in the Medical Profession, an attack on an established discipline in medicine includes four specific elements. The critic:

must portray the discourse as in crisis, must provide an alternative ideology to rescue the discourse, must legitimize their ideology through appeal to a reframed historical myth, and must portray the orthodoxy as a betrayer of the discourse.

Mbeki had no trouble representing the AIDS epidemic as a crisis of historic proportions. Anyone could daily witness the horrible toll in illness and lives lost. As Wolpe points out, the critic “rarely paints its opponent in terms of benign neglect”, but, rather, claims that it is evil. Therefore, Mbeki refuse to acknowledge that the AIDS epidemic is a plague like other historical plagues. Instead, he insisted, according to the New York Times that:

powerful vested interests — drug companies, governments, scientists — pushed the consensus view of AIDS in a quest for money and power, while peddling centuries-old white racist beliefs that depicted Africans as sexually rapacious.

Such claims represent the reframed historical myth to which Wolpe referred. Building on the deep seated and justified suspicion of colonialism, Mbeki portrayed AIDS, not as an infectious disease, but as an opportunity for drug companies run by white men to force toxic drugs on black people.

According to Chigwedere and colleagues, over 300,000 people died because Mbeki rejected the medical explanation for the origin and treatment of AIDS. It is important to understand that Mbeki did not simply deny the medical explanation; he crafted an ideological attack that was meant to replace the medical explanation. According to Mbeke, there was no need for his country to accept and distribute donated antiretroviral medications. Indeed, he believed that his people should fear the medication as nothing more than an attempt of drug companies to push toxic and unneeded treatments in an effort to make money.

Although Mbeki’s AIDS denialism was played out on a far larger scale, and hurt many more people, it has much in common with other popular claims of alternative medicine such as vaccine rejectionism, supplements as treatment or prevention for disease, and homebirth advocacy. All are political ideologies unmoored from the science of medicine. All are efforts to reframe what believers consider to be historical myths, and all characterize medical orthodoxy as a thinly disguised effort of companies or organizations to profit by pushing treatments that are both ineffective and harmful.

Ultimately, alternative medicine is about the flattering portrait proponents wish to draw of themselves. According to Wolpe, whether it is AIDS denialism or vaccine rejectionsism, it is always characterized as:

… the inevitable (or desirable) next step in the history of medicine, and like other heroes of medical history who were initially rejected by the orthodoxy of the day (Pasteur, Semmelweis, Sister Kenny) the [proponent] is simply ahead of his time. Innovation is always initially resisted, they argue, and since their practice causes no harm and brings greater patient satisfaction, it is also true to the ethic of safe practice. Holistic heretics portray themselves as mavericks, leaders, with every expectation that soon all of medicine will, by necessity, follow in their footsteps.

There is no doubt that Mbeki was sincere in his beliefs, and hundreds of thousands of people died as a result. Proponents of alternative medicine are almost always sincere in their beliefs, but alternative medicine is not science, it is ideology. Its false characterization of illness and treatment inevitably hurts people, at a minimum by depriving them of effective care. Mbeki and the results of his policy of AIDS denialism should serve as a cautionary tale for anyone who advocates replacing science with alternative medicine.

A new study in the Archives of Internal Medicine has been getting a lot of attention for its extraordinary claim that breast cancer can spontaneously disappear without any treatment. If it’s true, it raises a host of important questions: Should some women with breast cancer forgo toxic treatments? How does cancer simply disappear? Should we stop aggressive breast cancer screening?

The operative word, of course, is “if.” The case of the disappearing breast cancers described in the scientific paper is powerful but entirely circumstantial. The authors did not see even a single cancer disappear. They hypothesized that some breast cancers disappeared because they did not find as many cancers as they expected.

The paper is The Natural History of Invasive Breast Cancers Detected by Screening Mammography written by Zahl, Maehlan and Welch. The authors recruited over 200,000 Norwegian women ages 50-64 and divided them into two groups. The tested group had mammograms every other year for 6 years (a total of 3 mammograms). The control group had only one mammogram at the end of the 6 year period. The authors were very careful to make sure that the two groups were as similar as possible.

Over the course of the 6 year interval, 1909 cases of breast cancer were diagnosed per 100,000 women who had screening in every other year. In contrast, only 1564 cases of breast cancer were diagnosed per 100,000 women who had only one mammogram at the end of the 6 year interval. The authors concluded that over 300 cases of breast cancer were “missing” from the control group and they believe that those cancers arose and spontaneously disappeared.

Is that what really happened? First, we must consider the fact that the 1564 cases diagnosed in the control group does not include all cancers in the group. Screening mammography is not perfect and some cancers will be missed that might be detected on a subsequent scan.

Second, the use of estrogen replacement therapy in the study group was substantially higher than in the control group. Since hormone therapy has been associated with increases in breast cancer risk, that may account for part of the observed difference.

Third, the incidence of breast cancer in Norway increased over the life of the study. The women in the study group (1996-2002) had a known higher incidence of breast cancer than the women in the control group (1992-1998).

Even taking these factors into account, there is almost certainly a real difference in the cumulative number of breast cancer cases between the study group and the control group. In other words, routine mammography may over diagnose breast cancer by finding cancers that would disappear on their own if not treated.

That’s not a surprising finding. The body has many mechanisms for controlling the growth of runaway cells that could lead to cancer. The appearance of an actual cancer represents a failure of these mechanisms. It is possible, particularly in the case of small cancers detectable only by mammography, that there is still one last fail safe mechanism that could even then attack the tumor and destroy it. This study may be demonstrating that phenomenon.

There are some serious limitations to this study. The study only looks at incidence of cancer. It does not look at outcome and life expectancy. If it turns out that the women in the study group have a much lower incidence of death from breast cancer, because they are treated early and aggressively, it will justify the apparent over diagnosis of breast cancer. That is a very real possibility, because the data show that although the cumulative incidence of breast cancer in the control group was lower, many cases of breast cancer in the control group were not diagnosed until the mammogram at the end of the 6 years.

Finally, and most importantly, there is no way to tell the difference on mammography, or by any other technique, between the cancers that will disappear and the ones that will go on and kill the woman. Without a practical way to separate those who need to be treated from those who do not, the finding is intriguing and worthy of further investigation, but cannot guide us in determining the best way to screen for breast cancer and the best way to treat it.

 

 Yesterday’s Washington Post Magazine featured a thought-provoking article on the making of an abortion provider. Leaving aside the personal safety issues, which are large, the author chose to focus on the reality of performing abortion procedures and caring for the women who request them. It turns out that wanting women to have access to abortion and being personally willing to provide the service are two entirely different things.

According to the Guttmacher Institute, the premier advocacy group devoted to reproductive health and rights, the number of abortion providers remained relatively stable, dropping only 2% between 2000-2005. In contrast, provider numbers dropped 14% from 1992–1996 and 11% in 1996–2000. The primary reason why the number of providers stabilized is because the decrease in providers willing to perform surgical abortions was almost completely offset by the increase in providers offering new medical methods of pregnancy termination like RU-486.

Surgical abortions remain the mainstay of abortion provision, however, and increasing numbers of clinicians simply don’t want to perform them. The WaPo profile of a medical student activist committed to providing abortion procedures who ultimately changes her mind offers a unique insight into the difficulty of recruiting a new generation of providers. Simply put, the reality of providing abortions is far more unpleasant than the reality of supporting abortion rights.

Author Patricia Meisol introduces us to medical student Lesley Wojick:

a 24-year-old second-year medical student at the University of Maryland School of Medicine who had helped organize this regional student-hosted, daylong abortion seminar last year. Lesley respected forthrightness and unconventional thinking…

She had joined Medical Students for Choice, an abortion education group with chapters on 135 U.S. campuses, as soon as she arrived at Maryland. The nation’s abortion doctors were graying, and unless a new generation took their place, the right to abortion might be rendered meaningless. Lesley imagined herself being part of that new generation. But would her support for abortion translate into action?

“I won’t know until I’m faced with doing it, but I think I would absolutely be able to provide [abortions],” she said. “It’s walk the walk, instead of talk the talk. I want my actions to be consistent with my words.”

But Wojick finds that the reality of actually performing abortions is different than talking about them. According to the Guttmacher Institute, 1.2 million abortions were performed in 2005, down slightly from previous years. Although medical abortions are now widely available, they are not popular. Many women show up too late in pregnancy to qualify for medical abortions, and even those that are eligible usually choose surgical abortion because it is quicker and less painful.

Abortions rights supporters often portray abortion as a choice of last resort after contraceptive failure, but the reality is very different. Most women who seek abortions were not using birth control. The typical woman seeking an abortion is an unmarried woman in her 20’s who already has one or more children, and did not want another but took no precautions to prevent pregnancy. The grinding reality of abortion is that it is a method of birth control, not a last ditch effort to deal with a contraceptive failure.

The reality of the surgical procedure itself is even more jarring. At first Lesley feels that she can handle it. After watching a second trimester abortion she reports:

“It was definitely gruesome,” she said. “You could make out what a fetus could look like, tiny feet, lungs, but it didn’t look like a person.” She knew this abortion was an act that her friend … considered tantamount to murder. She herself expected to be very upset. She’d felt that way at her first autopsy, that of a teenage boy who’d shot himself in the head. For weeks, she could not shake the image of the boy. But this was different. She didn’t regard the fetus as a person yet. She said she was happy to help the woman: “I feel like I was giving [her] a new lease” on life.

Over time, though, Lesley begins to feel differently:

As for obstetrics … Lesley hadn’t loved very much about it. Even as she’d shadowed the abortion doctor, Lesley knew in her heart that this would not be the right place for her to make a difference. It was a big disappointment, she said. “I really thought I’d love it.”

The things she cared about — taking care of women, seeing them through the process — hadn’t happened. It was the nurse practitioner who cared for the patient. Vacuuming out a uterus and counting the parts of the fetus did not seem like a desirable way to spend her work days. It took a unique person to do that on a daily basis, she said.

The ongoing decline in abortion providers is a serious problem, threatening the access for women to a service that is entirely legal. On the other hand, the reality of abortion itself, used as a method of birth control, not as a last resort, and the unpleasant nature of the procedure, vacuuming out a uterus and counting the parts of the fetus, lead students like Lesley to change their minds. It’s one thing to support abortion rights; it’s entirely different to actually perform abortions.

Early in my internship I cared for a young Southeast Asian man who had a rare collagen disease. Surgery for an aneurysm (weakening in the wall of a blood vessel) in his pelvis left him with a large, poorly healing wound in his lower abdomen. As the lowliest member of the surgical team, it was my job to debride his wound every day. Debriding means cleaning and carefully removing any dead tissue from a wound. It would have been a lot easier for him and for me if I had had maggots.

 

 Maggots weren’t available then, but they are now. In a sign that maggots have gone mainstream, the government recently announced that Medicare and Medicaid will pay for maggot therapy. This is yet another milestone in the rise, fall and resurgence of maggots in medicine.

For centuries, maggots were an important part of wound care. According to Maggot Therapy: The Science and Implication for Complementary and Alternative Medicine:

… In 1829, Baron Dominic Larrey, Napoleon’s battlefield surgeon, described how men had arrived at his field hospital with healing maggot-infested wounds. The wounds were sustained in battle, but, owing to the presence of maggots, were not infected and showed accelerated healing. Such positive accounts were made by many surgeons who followed, but it was William Baer, Professor of Orthopaedic Surgery at the John Hopkins School of Medicine .., who is believed to be the founder of modern maggot therapy.

… Baer … pioneered the use of sterile maggots as a reputable method of wound therapy, following observations he made about the value of maggots in traumatic wounds on the battlefield in France during World War 1… [B]y the mid-1930s almost 1000 North American surgeons employed maggot therapy and by the end of the decade it was in use in over 300 hospitals in the US and Canada.

Instead of daily wound cleaning and removal like my patient had to endure, wound patients had a “dose” of maggots applied to the wound and the world’s tiniest “surgeons” did the same job, slowly and without patient discomfort, working 24/7 to heal wounds in record time.

Maggot therapy came to an abrupt end in the 1940’s when antibiotics came into widespread use. Antibiotics were easier to use, extraordinarily effective at healing infected wounds, and had greater scientific glamour than the lowly maggot. In an age of increasing antibiotic resistance, and the rise of “superbugs” such as MRSA (methicillin resistant staph aureaus), maggots are making a comeback.

Of course, not any maggots will do. The larvae of Phaenicia sericata, the common green-bottle fly, is the maggot of choice. That’s because maggots can be divided into two types, those that will eat living tissue and those that can only survive on dead tissue. Phaenicia maggots belong to the second type. In a wound, they will only consume the dead tissue that is interfering with healing and leave the live tissue alone. When there is no dead tissue left and the wound is healed, they will simply move on.

Maggots have some terrific advantages in wound healing. First, they seem to be able to do the job when all else fails. In Maggot debridement therapy of infected ulcers: patient and wound factors influencing outcome – a study on 101 patients with 117 wounds, the authors report:

It has been known for centuries that maggots are potent debriding agents capable of removing necrotic tissue and slough. … [W]e performed a prospective study to gain more insight in patient and wound characteristics influencing outcome…

… In total, 78 of 116 wounds (67%) had a successful outcome. These wounds healed completely (n = 60), healed almost completely (n = 12) or were clean at least (n = 6) at last follow-up. These results seem to be in line with those in the literature. All wounds with a traumatic origin (n = 24) healed completely… Outcome was not influenced by gender, obesity, diabetes mellitus, smoking, ASA-classification [wound severity], location of the wound, wound size or wound duration.

Second, maggots are effective when antibiotics fail. In the age of the “superbug,” bacteria that are resistant to multiple powerful antibiotics, maggots can still get the job done. Recent research has shown that maggots are just as effective in cleaning wounds caused by MRSA as they are at cleaning wounds caused by other bacteria. When the maggots remove the dead tissue, the body can heal the infection itself.

Third, using maggots to treat routine wounds instead of the current treatment with antibiotics would slow the rise of new drug resistant bacteria.

Finally, maggot therapy is much less expensive than conventional antibiotic therapy. A supply of “medical maggots” from Monarch Labs costs less than $100, in contrast to thousands of dollars for a course of powerful antibiotics. Maggots often work faster than antibiotics, reducing hospitalization costs. When you consider that maggots can prevent the need for amputation of limbs, a course of maggot therapy can save tens of thousands of dollars.

It’s not everyday that scientists discover a new treatment that is effective, easy to use, impervious to antibiotic resistance and inexpensive. The maggot, only recently relegated to the medical sidelines, is poised regain respect. That’s seems only fitting for what are, in truth, the world’s tiniest surgeons.