Informed Consent and the Ethics of DNA Research

[Guest guest]

http://www.nytimes.com/2010/04/25/weekinreview/25harmon.html?pagewanted=2

The cultural gap between the impoverished Havasupai Indians who view their blood

as sacred and the Arizona State University researchers who helicoptered in to

their Grand Canyon home to collect it was at the heart of a lawsuit over the

scope of a genetic study that ended last week with a settlement for the tribe.

But the case, scientists and bioethicists said, serves as a cautionary tale

about the equally significant gap between scientists and all research subjects,

who often seem to hail from different cultures even when the surface differences

are less apparent.

As troubling questions, some involving other lawsuits, have surfaced recently

among a range of research subjects who have learned that their genetic material

is being used in ways they weren¡¦t consulted about, scientists are debating how

to better apply the principle of ¡§informed consent¡¨ to large-scale genetic

research. At stake, they say, is the success of such research, which relies on

voluntary participation by increasingly large numbers of human subjects.

Some have proposed an international tribunal akin to the Helsinki human rights

agreement, which would lay out the ethical obligations to research participants.

Others suggest staying in touch with subjects so they can be consulted on new

projects ¡X and because under current practices they tend to learn of

breakthroughs based on their own DNA only if they become close readers of

scientific journals.

Courts have ruled that individuals do not have a property right to their cells

once they are taken in the course of medical care, but they do, under federal

guidelines, have a right to know how they will be used. Complicating matters is

the increasing impossibility of ensuring that DNA data can remain anonymous. Do

participants need to be told that their privacy cannot be guaranteed? Can

¡§blanket¡¨ consent up front do the trick, or is even that misleading because

researchers can¡¦t adequately describe the scope of studies they have yet to

design? Is it O.K. to use DNA collected for heart research to look for genetic

associations with intelligence, mental illness, racial differences?

For one thing, ¡§we have to communicate a hell of a lot better to the public

what is going on when we put their specimens in our biobanks,¡¨ said J.

O¡¦Brien, a geneticist who runs the Laboratory of Genomic Diversity at the

National Institutes of Health.

At issue in the Havasupai case was whether an Arizona State geneticist had

obtained permission from tribal members to use their DNA for anything other than

finding clues to Type 2 diabetes. More than 200 of the 650-member tribe signed a

consent form stating that their blood could be used to ¡§study the causes of

behavioral/medical disorders,¡¨ but many said they had believed they were

donating it only for the study of diabetes, which tribal members suffer from at

extraordinarily high rates.

When they learned years later that the DNA samples had been used to investigate

things they found objectionable, they felt betrayed. Researchers had

investigated genes thought to be associated with schizophrenia, a condition the

tribe considered stigmatizing, and traced the tribe¡¦s ancestral origins to

Asia, contradicting traditional stories holding that the Havasupai had

originated in the Grand Canyon.

Dr. O¡¦Brien said he sympathized with the position of Dr. Therese Markow, the

geneticist who had overseen the research at Arizona State and who insisted she

had received consent from her subjects. But it was her responsibility, Dr.

O¡¦Brien added, to make sure her subjects actually understood.

He noted that a similar question arose much more recently about what should be

done with some 200,000 DNA samples that government-funded scientists had

collected for studies of specific diseases. His own laboratory, for instance,

has gathered DNA from thousands of AIDS patients who gave permission for it to

be used in studying the genetics of H.I.V.

Should the samples be made available in a public database, so other federally

funded researchers can use them for additional studies? After all, they were

collected at considerable taxpayer expense. On the other hand, what if patients

disliked the purposes it was used for?

¡§What if someone decides to use them to look for a gene for homosexuality?¡¨

Dr. O¡¦Brien said. ¡§They might be pretty surprised to learn that.¡¨

Most likely they would never find out. (The Havasupai learned of the research

Dr. Markow had done only because another professor at the university made a

tribe member aware of it.) But what if they did find out?

That happened in Texas, when a newspaper report tipped parents off to the fact

that the drops of blood taken from newborns in the hospital for screening in

state laboratories ¡X a legally mandated practice that can stave off disease and

save lives ¡X were being stored and made available to scientists for other

research.

¡§The irony is if you had asked me, I probably would have consented,¡¨ said

Beleno, a legal aid attorney in Austin, Tex., who was among those who

sued the state health agency. ¡§I would love for there to be a cure for breast

cancer, which runs in my family. I would love for there to be a cure for

diabetes. The way the state went about it just made me distrustful.¡¨

It didn¡¦t help to learn from another newspaper report, after the state settled

the case, that some of the samples had been provided to a database used by the

military to improve the interpretation of forensic DNA evidence.

¡§I¡¦m not much of a conspiracy theorist,¡¨ said Ms. Beleno. ¡§I would have

laughed if someone said the state has a multimillion-person DNA database and

they¡¦re sending samples to the U.S. military.¡¨

The state¡¦s resulting decision to destroy the samples, legal advocates said,

was a loss for science that could have been prevented.

Some marginalized groups have shied away from genetic research for historical

reasons like the infamous Tuskegee syphilis study on African-Americans. As a

result, said Marcus Feldman, a Stanford geneticist, those who may have the least

access to medical care are also those whose genetics scientists know the least

about.

Studies have estimated that most individuals ¡X perhaps more than 90 percent ¡X

are willing to allow their data to be used for a range of biomedical research.

It is when they are not asked that problems arise.

Skloot, author of a book that recounts how cells taken by doctors from a

black woman with cervical cancer in the 1950s became a vital tool for medicine,

said people ask at every stop on her book tour how they can find out what is

being done with the blood or biopsy they may have left at a hospital.

¡§There is this sense of, ¡¥it¡¦s a piece of my body, and I want to know what¡¦s

happening to it,¡¦ ¡¨ said Ms. Skloot, whose book, ¡§The Immortal Life of

Henrietta Lacks,¡¨ has become a best seller.

Some advocates for patients have criticized a paternalism among scientists who

may tend to believe they are working to benefit humanity and prefer not to slow

down, or spend grant money, to explain their work. But part of the problem may

also be that communicating with the public is not what scientists are trained to

do.

¡§If you go to a hospital and you don¡¦t speak English, you¡¦re going to get a

translator,¡¨ said Ms. Skloot. ¡§If you go to the hospital and you don¡¦t speak

science, you¡¦re not, and in a way, that¡¦s what people need.¡¨

For pragmatic reasons and ethical ones, some researchers are trying out new

models. In pursuit of the huge volume of research participants that appear to be

necessary to find the many gene variants that contribute to common diseases like

diabetes, the Children¡¦s Hospital Boston, for instance, is pioneering a project

that lets researchers report whatever they find directly to the subjects, a

practice that has been considered impractical in the past, and fraught with

ethical issues of its own.

With that as incentive, they hope to enroll nearly every family that walks

through the door in a study that makes their medical records, as well as their

DNA, available to researchers.

Over the first six months of the project, genetic counselors have spent as much

as an hour with each family.

We talked a lot about how this kind of information can be shocking and

nerve-racking, and the things people can find out,¡¨ said Chellamal Keshavan,

21, a senior at Wheelock College in Boston. Then, readily, she gave her consent.