A new high-tech, grassroots effort to fight breast cancer

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I wrote this article for Slate’s Tech blog, Future Tense, after hearing about it from Joanna Rudnick, my close friend and one of the leaders of the project. You can see the article, which ran June 25, 2013 on Slate’s website here.

free the dataBy now you’ve probably heard that, thanks to the Supreme Court, no one, and certainly not Myriad Genetics, can patent human genes. This decision was sensible and long overdue, but the celebrations have been short-lived. Because what you may not have heard is that Myriad still owns all of the information it has collected since the mid-1990s on the breast cancer genes—and it has no intention of releasing any of it.

Myriad’s interpretations of mutations are out there, but scattered in a million pieces—in the reports it has sent out to women, or, more often, to the clinical centers where they were tested. But a new volunteer grass-roots effort, led by a few women with a family history of breast cancer, is trying to Free the Data so that scientists everywhere can analyze it and help women make informed choices about their breast-cancer risk. In collaboration with the University of California-San Francisco, the nonprofit advocacy group Genetic Alliance, and a biotech company InVitae, these women are hoping to collect even a tiny fraction of the million or so reports Myriad has sent out over the past 17 years.

Read the full article on Slate.

Controversy over cervical cancer vaccine

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(This article was #26 in Discover Magazine’s top 100 stories of 2007.)

This past year, several countries and at least 24 states in the United States introduced laws to mandate vaccination against cervical cancer for preteen girls. Although the vaccine was initially hailed as a breakthrough, urgent proposals to make it mandatory quickly triggered a backlash. “In the long term,” says Susan Wood, a former director of the FDA Office of Women’s Health, “the rush to get this mandated immediately has done more harm to the issue.”

The FDA approved Merck’s Gardasil vaccine in 2006, after clinical trials showed that it protects against four strains of human papillomavirus (HPV), which together cause about 70 percent of cervical cancers and 90 percent of genital warts. HPV is the most common sexually transmitted virus among Americans (and cervical cancer is the second most common cancer in women worldwide). Because the vaccine doesn’t reverse existing exposure, the CDC recommends it be administered before the age of sexual activity—specifically to girls ages 11 to 12. As for women who already have HPV, two separate studies published in May in the New England Journal of Medicine reported that the vaccine’s effectiveness in preventing cervical lesions dropped to 20 percent or less.

Some conservative groups oppose targeting preteens, arguing that because the virus is sexually transmitted, the vaccine will encourage promiscuity. Meanwhile, bioethicists who are skeptical about compulsory vaccination laws note that all other mandated vaccines protect against diseases easily transmitted in schools. “In my opinion, there’s not a compelling ethical reason [to mandate],” says Richard Zimmerman, professor of family medicine at the University of Pittsburgh. “The ethics is the opposite: to strongly recommend, but not to mandate.”

Risky business

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(This Opinion column ran on Nature’s news site on August 21, 2007. You can download a pdf of the post.)

It’s not the technology of gene therapy but the regulation of clinical trials that we should be most afraid of, says Apoorva Mandavilli.

Almost exactly seven years after the first death in a gene-therapy trial, another unexpected death hit imagesthe field late last month – followed quickly by panic, outrage and some calls for an end to gene therapy altogether.

But to blame and ban all gene therapy because of this would be rash and misguided. And it might risk missing the point. What we should be most outraged and scared by is the way this trial took place — and the similar mis-steps that seem to accompany a vast number of clinical trials, gene therapy or no gene therapy.

On 2 July Jolee Mohr, a 36-year-old woman in Chicago, received an injection she thought would treat her painful — although not debilitating — arthritis. She died on 24 July of multiple organ failure, which was also the cause of death of 18-year-old Jesse Gelsinger in September 1999. In each case, the US Food and Drug Administration responded by suspending the trial and any others that used a similar approach.

But tragic and avoidable as both deaths were, I think we should be more worried about a broken system for clinical trials than of a risky treatment.

Don’t rush your vaccines

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(This Opinion column ran in Nature’s news site on May 17, 2007. You can read the original post here.)

The ethical debate about a vaccine for a sexually transmitted disease has been premature, says Apoorva Mandavilli; we don’t even know how well it works.

Here’s a good lesson: before you start pushing for a controversial vaccine to be made compulsory, HPV vaccinebest wait for the research — and I mean all the research — to come up with results.

For more than a year, we’ve been hearing that there is a vaccine that is 100% safe and effective in protecting young girls and women from the deadly viruses that cause cervical cancer.

Merck’s Gardasil, a vaccine against human papilloma virus (HPV), has been hailed as perhaps the biggest boon for women since the contraceptive pill. Across the world, including many American states, politicians and activists have proposed laws to make Gardasil mandatory for girls in their early teens or younger. Australia has already started a national programme of free vaccines for young girls.

All that sounds a bit premature — and rightly so. As we find out more about this vaccine, including new studies in last week’s New England Journal of Medicine1,2, it’s clear we simply don’t know enough about it to be giving it to young girls en masse.

Held to ransom

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(This Opinion column ran on Nature’s news site on March 26, 2007. You can download a pdf of the original post.)

A pharma giant’s decision to withhold new drugs from Thailand will only hurt patients, says Apoorva Mandavilli.

Is there ever a good enough reason to deny life-saving medicines to an entire country’s citizens? I say no. But it seems pharmaceutical giant Abbott begs to differ.

The Chicago-based company decided on 14 March not to introduce in Thailand any of its seven new drugs — including an antibiotic, an important AIDS drug called Kaletra and medicines to treat blood clots, kidney disease and high blood pressure. Without this crucial registration, the drugs cannot be imported to or sold in that country.

It seems to me that Abbott is, in effect, holding millions of Thais’ lives hostage to force their government to respect its patents. This is good business?

The price of drugs varies from place to place.

The price of drugs varies from place to place.

What’s shocking to me is that the company is making no bones about the fact that its decision is retaliation against Thailand’s decision in January to issue ‘compulsary licenses’ allowing some locals to import or make cheap copies of Abbott’s new version of Kaletra. “This matter is about intellectual property and the integrity of the patent system,” Abbott spokeswoman Melissa Brotz said in a statement.

Lofty words, but I’m reminded more of a schoolyard fight.

Big issues from a small child

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(This Opinion column ran on Nature’s news site on January 8, 2007. You can read the original post here.)

How far can a parent go in managing the life of their disabled child? Perhaps too far.

Shock. Even revulsion. These were the main reactions provoked by news stories about Ashley, a nine-year-old disabled girl who has been surgically and hormonally altered by her parents to forever stay the size of a small child. Is such treatment acceptable, asked the world’s press. On instinct, my immediate reaction was “no”.Ashley2006

But instinct isn’t always a good judge of sensitive ethical issues. So I learned more about the situation. The shock has now subsided. But my answer to the question of acceptability is still “no”, albeit for different reasons.

Keeping a child small to help her parents care for her is an untested medical solution to a societal problem — and one that could set a dangerous precedent.

Premature medication

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(This Opinion column ran on Nature’s news site on December 22, 2006. You can see the original post here.)

Handing out experimental drugs to desperate patients is not a good idea, says Apoorva Mandavilli.

At first glance it seems only kind and right to let people with serious illnesses take whatever medicines they want. Some have campaigned so hard for this that the US Food and Drug Administration agreed on 11 December to let patients buy experimental drugs direct from the manufacturer when there are no other options available.

But this could have some terrible consequences.

Yes, the humanitarian argument for giving access is compelling. And yes, on an individual basis, it seems cruel to deny a medicine to someone who is suffering. But if the drug hasn’t been properly tested, how do we know it won’t aggravate the illness or, worse still, prove fatal to the people who take it? It may even actively discourage companies from investing in proper trials for those drugs where the only customers are desperate patients.

Actions speak louder than images

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(This article appeared in the 7 December, 2006 issue of Nature.)

Handle with care: can brain scans really identify antisocial people?

Can brain scans of a racist, liar or psychopath accurately tell whether that person will persecute, fib or kill? No, say experts in the ethics of neuroscience, who are increasingly concerned that such images will be used to make dangerous legal or social judgements about people’s behaviour. They say it is time for scientists, lawyers and philosophers to speak up about the limitations of such techniques.

“Lawyers want to know ‘Can I put somebody on the scanner and tell if they’re racist?’” says Elizabeth Phelps, a psychologist and neuroscientist at New York University who has studied the brain’s response to race. “We as 
a group of scientists have to be 
able to say that we can’t make that distinction.” Phelps spoke at a panel discussion on the emerging field of neuroethics held in New York last week.

Finally: hints of HIV turnaround in South Africa

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(This Opinion column ran on Nature’s news site on November 3, 2006. You can see the original post here.)

It’s about time that this country hard-hit by AIDS promised help for the afflicted, says Apoorva Mandavilli.

aids-in-southafrica-grafitiHIV causes AIDS. That’s not news to you or me, but shockingly it has taken years for the government in South Africa — where about 1,000 people die of AIDS every day — to acknowledge that fact and pledge to provide medicines.

In the past few weeks, the country’s deputy president Phumzile Mlambo-Ngcuka has publicly promised to expand access to AIDS tests, antiretroviral drugs and prevention programmes to those who most need them.

That sounds sensible — if a rather obvious thing for a politician to say — but it’s a far cry from what South Africans had heard until recently.

Health minister Manto Tshabalala-Msimang has extolled the virtues of beetroot, lemon juice and garlic in fighting AIDS. At the international AIDS conference in Toronto this August, her booth prominently featured those items. Six years earlier, at the same conference in Durban, President Thabo Mbeki said he didn’t know anyone with AIDS and questioned its link to HIV.

It’s about time the government changed its tune. As the richest country in Africa, South Africa is in a much better position to combat AIDS than its poorer neighbours. But thanks to the government’s appalling neglect, it hasn’t seen any decline in the rate of new infections.

DDT returns

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I wrote this article for Nature Medicine in July 2006. This was a big scoop. The news flew mostly under the radar, with the big announcement due that September. But I had heard rumblings of it at conferences, and was able to get fantastic access to (and quotes from) Arata Kochi, then head of the WHO’s malaria program. You can download a pdf of this article.)

The most infamous pesticide in history is also the most effective weapon against malaria. Ready or not, DDT is on its way back to Africa. Apoorva Mandavilli reports.

It’s possibly the most reviled chemical on the planet. Every adult anywhere in the world could list its supposed evils. And it’s been the subject of a long and bitter battle that defies traditional divisions of liberal and conservative.

But here it is, poised for a comeback.

After decades of being marginalized as a dangerous pesticide, DDT—short for dichloro-diphenyl-trichloro ethane—is set to be reintroduced into countries that have tried, and failed, to win the fight against malaria.

Big impact: Small amounts of DDT sprayed on walls can help control malaria.
Afp photo Alexander Joe
Natalia Soto / LN

On 2 May, the United States Agency for International Development (USAID), arguably the most powerful donor agency in the world, endorsed the indoor spraying of DDT for malaria control. The World Health Organization (WHO) is set to follow. In its new guidelines, a final version of which is expected to be released later this summer, the WHO is unequivocal in its recommendation of DDT for indoor residual spraying.

For the many African countries riddled with malaria, this is welcome news. “We in southern Africa feel extremely happy,” says John Govere, integrated vector control officer for the WHO’s Southern Africa Malaria Control Programme.

Malaria kills as many as 1 million people each year, about 90% of them in Africa. Someone dies of malaria every 30 seconds—and most of those are pregnant women and children under the age of five. Even the millions who survive can be reinfected, leaving them bedridden and decimating economies.

Little surprise then, that just days after USAID’s announcement, Tanzania said that it would lift its DDT ban. Others soon followed.

For these impoverished countries, the choice may seem clear: DDT is cheap and lasts longer than other pesticides, so it has to be sprayed less often. Most pesticides work by killing mosquitoes on contact, but DDT also repels them.

“DDT is the most effective chemical, the most effective insecticide in terms of malaria,” says Arata Kochi, director of the WHO’s Global Malaria Programme.

Silent spring
If DDT is that effective, why has it been so vilified? “You’ve heard of Rachel Carson? Well that’s your answer,” says Maureen Coetzee, chief of vector control research at South Africa’s National Institute for Communicable Diseases. “DDT was so abused in the ’50s and ’60s that it is still suffering from that abuse.”

In the 1940s, DDT was considered a miracle chemical. Airplanes sprayed thousands of tons of the pesticide, coating acres of crops, villages and cities with abandon.

By 1949, the US was malaria free. Between 1955 and 1969, the Global Malaria Eradication Campaign also relied heavily on DDT. In Europe, India, South America, Africa, wherever it was used widely, DDT cut malaria rates dramatically and saved millions of lives.

Then came Carson’s Silent Spring— credited with launching the environmental movement—which famously described DDT’s horrific effects on the food chain, and the stark silence left behind by dying birds. The book was so effective that to this day, any mention of DDT instantly evokes images of bald eagles and thinning eggshells.

DDT soon became a symbol of Western governments’ rash embrace of science. In the US and in Europe, environmental groups waged a successful campaign against the pesticide. Based largely on its effect on the environment—and on public opinion—the US Environmental Protection Agency in 1972 banned DDT. Norway and Sweden had begun the trend in 1970, and the UK signed on in 1986.

Environmental groups that still oppose DDT see its use in developing countries as a double standard. On the other hand, note champions of DDT, most of those groups are based in countries where malaria is only a distant memory.

“I think the whole push of the environmentalists like Rachel Carson and many others to eliminate all uses of DDT are, quite honestly, responsible for millions and millions and millions of human deaths,” says Don Roberts, professor of tropical public health at the Uniformed Services University of the Health Sciences in Maryland.

Money talks
In theory, any country is free to use DDT. The Stockholm Convention of 2001 sought a global ban on DDT, but many countries and scientists argued against the ban, citing its value in malaria control. The final treaty made an exemption for DDT’s use in public health, but called for countries to gradually phase out the pesticide.

Still, in places where malaria was still endemic, the treaty spelled disaster.

Most African nations are heavily dependent on foreign aid and can ill afford to cross a line drawn by donor agencies.

USAID never banned DDT outright, for instance, but nor did it fund DDT’s purchase—which amounts to the same thing. For that reason, the May announcement is widely seen as a change in policy even though the agency doesn’t position it as such.

The World Bank went one step further, making the ban of DDT a condition for loans. The WHO supported the use of bednets dipped in insecticide over indoor spraying, even though malaria rates continued to increase. DDT was “further ignored and intentionally or unintentionally suppressed,” by these agencies, says Kochi.

“People are very emotional about DDT, even within the WHO,” Kochi says, adding that much of the reaction to DDT was a response to political pressure. Since his arrival at the agency in late 2005, he has pushed for the return of indoor spraying not just to Africa, but wherever malaria continues to be a problem.

The WHO plans to field test its new guidelines for indoor residual spraying in Yemen, Sudan and two countries in south eastern Asia. “Quite often in this field, politics comes first and science second,” Kochi says. “We must take a position based on the science and the data.”

Disputed dangers

Watch out: In the 1940s, DDT was sprayed aerially for agriculture.
Associated Press

The WHO recommends 12 insecticides including DDT—which is an organochlorine—six pyrethroids, three organophosphates and two carbamates. In terms of toxicity to humans, DDT is considered safer than many of the others.

Because only small quantities are sprayed on the walls for malaria control, “unless you go and lick the wall, you’re not likely to ingest the insecticide,” notes Coetzee.

Over the years, however, based primarily on data from agricultural use, DDT has been linked to various illnesses—but those studies are rarely convincing and never consistent.

DDT was thought to cause liver and breast cancer and disrupt hormonal balance, for example, but the claims have since been debunked (Lancet356, 267–268; 2000; Nat. Med. 6, 729–731; 2000). Studies have found that in areas where DDT is sprayed for malaria control, mothers show traces of DDT in their blood and breast milk (Bull. World Health Organ. 68, 761–768; 1990). Some scientists say those levels might trigger premature births and a shorter time for breast-feeding (Lancet 366, 763–773; 2005), but the results are much disputed.

Most recently, researchers in California reported in July that babies of mothers exposed to DDT fare worse on mental tests and motor skills tests (Pediatrics 118, 233–241). But critics note that the study followed only 360 women and that because the mothers were born in Mexico—where DDT was used for agriculture till 1995—the researchers cannot link the exposure to malaria control.

But even critics of DDT agree that in countries ravaged by malaria, the benefits far outweigh the risks. “I’d rather have a child with three IQ points less than have a dead child,” says Brenda Eskenazi, lead researcher of the Mexico study.

Although DDT might be a short-term solution for malaria control, however, more research is needed before it can be regarded as entirely safe, Eskenazi and others caution.

For instance, when assessing DDT’s effect on malaria, global agencies should measure rates of total infant mortality, and not just malaria-related deaths, says Walter Rogan, an epidemiologist at the US National Institute on Environmental Health Sciences. That would help catch any adverse affects DDT may have on infant health, he says.

“I think that DDT is not entirely a benign compound,” Rogan says. “If you’re going to use it, you should consider the idea that it might do harm.”

Within walls
DDT’s use in malaria is far different from its application in agriculture. In contrast to indiscriminate aerial spraying several times a year, individuals spray a small amount—about two grams per square meter, a fraction of that used in agriculture—on the inside walls and eaves of houses, where mosquitoes rest.

Because DDT is not sprayed outdoors, there is little chance of it getting into the environment, notes Simon Kunene, chair of the malaria subcommittee for the Southern African Development Community (SADC).

But with thousands of tons of the cheap pesticide available, some of it will inevitably be diverted for agricultural use, experts warn.

“What concerns me a lot is that it’s going to be misused and end up in the environment,” says Mark Rowland, a malaria control expert at the London School of Hygiene and Tropical Medicine.

The WHO is considering a method that South Africa has developed over the years. Precise amounts of DDT are shipped from a central location to the area where they are needed, minimizing middlemen en route, and once spraying is complete, the containers are returned for checking.

But South Africa, with its relatively well-developed infrastructure, may be an exception, argues Rowland. From 1991 to 1998, Rowland led a malaria control program for Afghan refugees in Pakistan. That program employed a similar method, using packets of DDT that were closely supervised. Still, some packets were misused, Rowland says. “It’s very difficult to monitor every kilogram that gets distributed.”

Fine print
The best long-term prospect may be to develop safe and effective alternatives, several of which are being developed by public-private partnerships.

Meanwhile, the use of DDT, and of indoor spraying generally, is expected to rise sharply.

“People are now beginning to appreciate how effective indoor residual spraying can be,” says Richard Greene, director of the Office of Health, Infectious Disease and Nutrition in USAID’s Bureau for Global Health.

Unless done well, however, using DDT may be dangerous—and powerless against malaria.

For spraying to be effective, at least 80% of the affected area must be covered. Global agencies must first map the distribution and behavior of different kinds of mosquitoes and, most important, patterns of resistance to insecticides. “The last thing you want to do is select for resistance,” says Coetzee.

Convincing the local community to let people into their homes and spray their walls is another formidable challenge. At the height of the epidemic, people are generally terrified enough to do whatever it takes. But once the mosquitoes—and, as a bonus, the cockroaches—disappear, so does people’s tolerance.

Because DDT lasts longer than other pesticides—up to a year compared to six months with pyrethroids—it needs to be sprayed less often, making its use less challenging for governments.

“What can I say? It has worked for us,” says Kunene. “They’ll see the results. Give me one year or two years. There’ll be a big difference.”

Published online: 27 July 2006.