DNA


WHEN the police arrived last November at the ransacked mansion of the millionaire investor Raveesh Kumra, outside of San Jose, Calif., they found Mr. Kumra had been blindfolded, tied and gagged. The robbers took cash, rare coins and ultimately Mr. Kumra’s life; he died at the scene, suffocated by the packaging tape used to stifle his screams. A forensics team found DNA on his fingernails that belonged to an unknown person, presumably one of the assailants. The sample was put into a DNA database and turned up a “hit” — a local man by the name of Lukis Anderson.

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Bingo. Mr. Anderson was arrested and charged with murder.

There was one small problem: the 26-year-old Mr. Anderson couldn’t have been the culprit. During the night in question, he was at the Santa Clara Valley Medical Center, suffering from severe intoxication.

Yet he spent more than five months in jail with a possible death sentence hanging over his head. Once presented with Mr. Anderson’s hospital records, prosecutors struggled to figure out how an innocent man’s DNA could have ended up on a murder victim.

Late last month, prosecutors announced what they believe to be the answer: the paramedics who transported Mr. Anderson to the hospital were the very same individuals who responded to the crime scene at the mansion a few hours later. Prosecutors now conclude that at some point, Mr. Anderson’s DNA must have been accidentally transferred to Mr. Kumra’s body — likely by way of the paramedics’ clothing or equipment.

This theory of transference is still under investigation. Nevertheless, the certainty with which prosecutors charged Mr. Anderson with murder highlights the very real injustices that can occur when we place too much faith in DNA forensic technologies.

In the end, Mr. Anderson was lucky. His alibi was rock solid; prosecutors were forced to concede that there must have been some other explanation. It’s hard to believe that, out of the growing number of convictions based largely or exclusively on DNA evidence, there haven’t been any similar mistakes.

In one famous case of crime scene contamination, German police searched for around 15 years for a serial killer they called the “Phantom of Heilbronn” — an unknown female linked by traces of DNA to six murders across Germany and Austria. In 2009, the police found their “suspect”: a worker at a factory that produced the cotton swabs police used in their investigations had been accidentally contaminating them with her own DNA.

Contamination is not the only way DNA forensics can lead to injustice. Consider the frequent claim that it is highly unlikely, if not impossible, for two DNA profiles to match by coincidence. A 2005 audit of Arizona’s DNA database showed that, out of some 65,000 profiles, nearly 150 pairs matched at a level typically considered high enough to identify and prosecute suspects. Yet these profiles were clearly from different people.

There are also problems with the way DNA evidence is interpreted and presented to juries. In 2008, John Puckett — a California man in his 70s with a sexual assault record — was accused of a 1972 killing, after a trawl of the state database partially linked his DNA to crime scene evidence. As in the Anderson case, Mr. Puckett was identified and implicated primarily by this evidence. Jurors — told that there was only a one-in-1.1 million chance that this DNA match was pure coincidence — convicted him. He is now serving a life sentence.

But that one-in-1.1 million figure is misleading, according to two different expert committees, one convened by the F.B.I., the other by the National Research Council. It reflects the chance of a coincidental match in relation to the size of the general population (assuming that the suspect is the only one examined and is not related to the real culprit). Instead of the general population, we should be looking at only the number of profiles in the DNA database. Taking the size of the database into account in Mr. Puckett’s case (and, again, assuming the real culprit’s profile is not in the database) would have led to a dramatic change in the estimate, to one in three.

One juror was asked whether this figure would have affected the jury’s deliberations. “Of course it would have changed things,” he told reporters. “It would have changed a lot of things.”

DNA forensics is an invaluable tool for law enforcement. But it is most useful when it corroborates other evidence pointing to a suspect, or when used to determine whether any two individual samples match, like in the exonerations pursued by the Innocence Project.

But when the government gets into the business of warehousing millions of DNA profiles to seek “cold hits” as the primary basis for prosecutions, much more oversight by and accountability to the public is warranted. For far too long, we have allowed the myth of DNA infallibility to chip away at our skepticism of government’s prosecutorial power, undoubtedly leading to untold injustices.

In the Anderson case, thankfully, prosecutors acknowledged the obvious: their suspect could not have been in two places at once. But he was dangerously close to being on his way to death row because of that speck of DNA. That one piece of evidence — obtained from a technology with known limitations, and susceptible to human error and prosecutorial misuse — might mistakenly lead to execution at the hands of the state should send chills down every one of our spines. The next Lukis Anderson could be you. Better hope your alibi is as well documented as his.

By OAGIE K. OBASOGIE, New York Times, July 24, 2013

Osagie K. Obasogie, a professor of law at the University of California, Hastings, and a senior fellow at the Center for Genetics and Society, is the author of the forthcoming book “Blinded by Sight: Seeing Race Through the Eyes of the Blind.”

Our brains are better than Google or the best robot from iRobot.

We can instantly search through a vast wealth of experiences and emotions. We can immediately recognize the face of a parent, spouse, friend or pet, whether in daylight, darkness, from above or sideways—a task that the computer vision system built into the most sophisticated robots can accomplish only haltingly. We can also multitask effortlessly when we extract a handkerchief from a pocket and mop our brow while striking up a conversation with an acquaintance. Yet designing an electronic brain that would allow a robot to perform this simple combination of behaviors remains a distant prospect.

How does the brain pull all this off, given that the complexity of the networks inside our skull—trillions of connections among billions of brain cells—rivals that of theInternet? One answer is energy efficiency: when a nerve cell communicates with another, the brain uses just a millionth of the energy that a digital computer expends to perform the equivalent operation. Evolution, in fact, may have played an important role in pushing the three-pound organ toward ever greater energy efficiencies.

Parsimonious energy consumption cannot be the full explanation, though, given that the brain also comes with many built-in limitations. One neuron in the cerebral cortex, for instance, can respond to an input from another neuron by firing an impulse, or a “spike,” in thousandths of a second—a snail’s pace compared with the transistors that serve as switches in computers, which take billionths of a second to switch on. The reliability of the neuronal network is also low: a signal traveling from one cortical cell to another typically has only a 20 percent possibility of arriving at its ultimate destination and much less of a chance of reaching a distant neuron to which it is not directly connected.

Neuroscientists do not fully understand how the brain manages to extract meaningful information from all the signaling that goes on within it. The two of us and others, however, have recently made exciting progress by focusing new attention on how the brain can efficiently use the timing of spikes to encode information and rapidly solve difficult computational problems. This is because a group of spikes that fire almost at the same moment can carry much more information than can a comparably sized group that activates in an unsynchronized fashion.

Beyond offering insight into the most complex known machine in the universe, further advances in this research could lead to entirely new kinds of computers. Already scientists have built “neuromorphic” electronic circuits that mimic aspects of the brain’s signaling network. We can build devices today with a million electronic neurons, and much larger systems are planned. Ultimately investigators should be able to build neuromorphic computers that function much faster than modern computers but require just a fraction of the power [see “Neuromorphic Microchips,” by Kwabena Boahen; Scientific American, May 2005].

Cell Chatter

Like many other neuroscientists, we often use the visual system as our test bed, in part because its basic wiring diagram is well understood. Timing of signals there and elsewhere in the brain has long been suspected of being a key part of the code that the brain uses to decide whether information passing through the network is meaningful. Yet for many decades these ideas were neglected because timing is only important when compared between different parts of the brain, and it was hard to measure activity of more than one neuron at a time. Recently, however, the practical development of computer models of the nervous system and new results from experimental and theoretical neuroscience have spurred interest in timing as a way to better understand how neurons talk to one another.

Brain cells receive all kinds of inputs on different timescales. The microsecond-quick signal from the right ear must be reconciled with the slightly out-of-sync input from the left. These rapid responses contrast with the sluggish stream of hormones coursing through the bloodstream. The signals most important for this discussion, though, are the spikes, which are sharp rises in voltage that course through and between neurons. For cell-to-cell communication, spikes lasting a few milliseconds handle immediate needs. A neuron fires a spike after deciding that the number of inputs urging it to switch on outweigh the number telling it to turn off. When the decision is made, a spike travels down the cell’s axon (somewhat akin to a branched electrical wire) to its tips. Then the signal is relayed chemically through junctions, called synapses, that link the axon with recipient neurons.

In each eye, 100 million photoreceptors in the retina respond to changing patterns of light. After the incoming light is processed by several layers of neurons, a million ganglion cells at the back of the retina convert these signals into a sequence of spikes that are relayed by axons to other parts of the brain, which in turn send spikes to still other regions that ultimately give rise to a conscious perception. Each axon can carry up to several hundred spikes each second, though more often just a few spikes course along the neural wiring. All that you perceive of the visual world—the shapes, colors and movements of everything around you—is coded into these rivers of spikes with varying time intervals separating them.

Monitoring the activity of many individual neurons at once is critical for making sense of what goes on in the brain but has long been extremely challenging. In 2010, though, E. J. Chichilnisky of the Salk Institute for Biological Studies in La Jolla, Calif., and his colleagues reported in Nature that they had achieved the monumental task of simultaneously recording all the spikes from hundreds of neighboring ganglion cells in monkey retinas. (Scientific American is part of Nature Publishing Group.) This achievement made it possible to trace the specific photoreceptors that fed into each ganglion cell. The growing ability to record spikes from many neurons simultaneously will assist in deciphering meaning from these codelike brain signals.

For years investigators have used several methods to interpret, or decode, the meaning in the stream of spikes coming from the retina. One method counts spikes from each axon separately over some period: the higher the firing rate, the stronger the signal. The information conveyed by a variable firing rate, a rate code, relays features of visual images, such as location in space, regions of differing light contrast, and where motion occurs, with each of these features represented by a given group of neurons.

Information is also transmitted by relative timing—when one neuron fires in close relation to when another cell spikes. Ganglion cells in the retina, for instance, are exquisitely sensitive to light intensity and can respond to a changing visual scene by transmitting spikes to other parts of the brain. When multiple ganglion cells fire at almost the same instant, the brain suspects that they are responding to an aspect of the same physical object. Horace Barlow, a leading neuroscientist at the University of Cambridge, characterized this phenomenon as a set of “suspicious coincidences.” Barlow referred to the observation that each cell in the visual cortex may be activated by a specific physical feature of an object (say, its color or its orientation within a scene). When several of these cells switch on at the same time, their combined activation constitutes a suspicious coincidence because it may only occur at a specific time for a unique object. Apparently the brain takes such synchrony to mean that the signals are worth noting because the odds of such coordination occurring by chance are slim.

 

Electrical engineers are trying to build on this knowledge to create more efficient hardware that incorporates the principles of spike timing when recording visual scenes. One of us (Delbruck) has built a camera that emits spikes in response to changes in a scene’s brightness, which enables the tracking of very fast moving objects with minimal processing by the hardware to capture images [see box above].

Into the Cortex

New evidence adds proof that the visual cortex attends to temporal clues to make sense of what the eye sees. The ganglion cells in the retina do not project directly to the cortex but relay signals through neurons in the thalamus, deep within the brain’s midsection. This region in turn must activate 100 million cells in the visual cortex in each hemisphere at the back of the brain before the messages are sent to higher brain areas for conscious interpretation.

We can learn something about which spike patterns are most effective in turning on cells in the visual cortex by examining the connections from relay neurons in the thalamus to cells known as spiny stellate neurons in a middle layer of the visual cortex. In 1994 Kevan Martin, now at the Institute of Neuroinformatics at the University of Zurich, and his colleagues reconstructed the thalamic inputs to the cortex and found that they account for only 6 percent of all the synapses on each spiny stellate cell. How, then, everyone wondered, does this relatively weak visual input, a mere trickle, manage to reliably communicate with neurons in all layers of the cortex?

Cortical neurons are exquisitely sensitive to fluctuating inputs and can respond to them by emitting a spike in a matter of a few milliseconds. In 2010 one of us (Sejnowski), along with Hsi-Ping Wang and Donald Spencer of the Salk Institute and Jean-Marc Fellous of the University of Arizona, developed a detailed computer model of a spiny stellate cell and showed that even though a single spike from only one axon cannot cause one of these cells to fire, the same neuron will respond reliably to inputs from as few as four axons projecting from the thalamus if the spikes from all four arrive within a few milliseconds of one another. Once inputs arrive from the thalamus, only a sparse subset of the neurons in the visual cortex needs to fire to represent the outline and texture of an object. Each spiny stellate neuron has a preferred visual stimulus from the eye that produces a high firing rate, such as the edge of an object with a particular angle of orientation.

In the 1960s David Hubel of Harvard Medical School and Torsten Wiesel, now at the Rockefeller University, discovered that each neuron in the relevant section of the cortex responds strongly to its preferred stimulus only if activation comes from a specific part of the visual field called the neuron’s receptive field. Neurons responding to stimulation in the fovea, the central region of the retina, have the smallest receptive fields—about the size of the letter e on this page. Think of them as looking at the world through soda straws. In the 1980s John Allman of the California Institute of Technology showed that visual stimulation from outside the receptive field of a neuron can alter its firing rate in reaction to inputs from within its receptive field. This “surround” input puts the feature that a neuron responds to into the context of the broader visual environment.

Stimulating the region surrounding a neuron’s receptive field also has a dramatic effect on the precision of spike timing. David McCormick, James Mazer and their colleagues at Yale University recently recorded the responses of single neurons in the cat visual cortex to a movie that was replayed many times. When they narrowed the movie image so that neurons triggered by inputs from the receptive field fired (no input came from the surrounding area), the timing of the signals from these neurons had a randomly varying and imprecise pattern. When they expanded the movie to cover the surrounding area outside the receptive field, the firing rate of each neuron decreased, but the spikes were precisely timed.

 

The timing of spikes also matters for other neural processes. Some evidence suggests that synchronized timing—with each spike representing one aspect of an object (color or orientation)—functions as a means of assembling an image from component parts. A spike for “pinkish red” fires in synchrony with one for “round contour,” enabling the visual cortex to merge these signals into the recognizable image of a flower pot.

Attention and Memory

Our story so far has tracked visual processing from the photoreceptors to the cortex. But still more goes into forming a perception of a scene. The activity of cortical neurons that receive visual input is influenced not only by those inputs but also by excitatory and inhibitory interactions between cortical neurons. Of particular importance for coordinating the many neurons responsible for forming a visual perception is the spontaneous, rhythmic firing of a large number of widely separated cortical neurons at frequencies below 100 hertz.

Attention—a central facet of cognition—may also have its physical underpinnings in sequences of synchronized spikes. It appears that such synchrony acts to emphasize the importance of a particular perception or memory passing through conscious awareness. Robert Desimone, now at the Massachusetts Institute of Technology, and his colleagues have shown that when monkeys pay attention to a given stimulus, the number of cortical neurons that fire synchronized spikes in the gamma band of frequencies (30 to 80 hertz) increases, and the rate at which they fire rises as well. Pascal Fries of the Ernst Strüngmann Institute for Neuroscience in cooperation with the Max Planck Society in Frankfurt found evidence for gamma-band signaling between distant cortical areas.

Neural activation of the gamma-frequency band has also attracted the attention of researchers who have found that patients with schizophrenia and autism show decreased levels of this type of signaling on electroencephalographic recordings. David Lewis of the University of Pittsburgh, Margarita Behrens of the Salk Institute and others have traced this deficit to a type of cortical neuron called a basket cell, which is involved in synchronizing spikes in nearby circuits. An imbalance of either inhibition or excitation of the basket cells seems to reduce synchronized activity in the gamma band and may thus explain some of the physiological underpinnings of these neurological disorders. Interestingly, patients with schizophrenia do not perceive some visual illusions, such as the tilt illusion, in which a person typically misjudges the tilt of a line because of the tilt of nearby lines. Similar circuit abnormalities in the prefrontal cortex may be responsible for the thought disorders that accompany schizophrenia.

When it comes to laying down memories, the relative timing of spikes seems to be as important as the rate of firing. In particular, the synchronized firing of spikes in the cortex is important for increasing the strengths of synapses—an important process in forming long-term memories. A synapse is said to be strengthened when the firing of a neuron on one side of a synapse leads the neuron on the other side of the synapse to register a stronger response. In 1997 Henry Markram and Bert Sakmann, then at the Max Plank Institute for Medical Research in Heidelberg, discovered a strengthening process known as spike-timing-dependent plasticity, in which an input at a synapse is delivered at a frequency in the gamma range and is consistently followed within 10 milliseconds by a spike from the neuron on the other side of the synapse, a pattern that leads to enhanced firing by the neuron receiving the stimulation. Conversely, if the neuron on the other side fires within 10 milliseconds before the first one, the strength of the synapse between the cells decreases.

Some of the strongest evidence that synchronous spikes may be important for memory comes from research by György Buzsáki of New York University and others on the hippocampus, a brain area that is important for remembering objects and events. The spiking of neurons in the hippocampus and the cortical areas that it interacts with is strongly influenced by synchronous oscillations of brain waves in a range of frequencies from four to eight hertz (the theta band), the type of neural activity encountered, for instance, when a rat is exploring its cage in a laboratory experiment. These theta-band oscillations can coordinate the timing of spikes and also have a more permanent effect in the synapses, which results in long-term changes in the firing of neurons.

 

A Grand Challenge Ahead

Neuroscience is at a turning point as new methods for simultaneously recording spikes in thousands of neurons help to reveal key patterns in spike timing and produce massive databases for researchers. Also, optogenetics—a technique for turning on genetically engineered neurons using light—can selectively activate or silence neurons in the cortex, an essential step in establishing how neural signals control behavior. Together, these and other techniques will help us eavesdrop on neurons in the brain and learn more and more about the secret code that the brain uses to talk to itself. When we decipher the code, we will not only achieve an understanding of the brain’s communication system, we will also start building machines that emulate the efficiency of this remarkable organ.

 

* By Terry Sejnowski and Tobi Delbruck  

ABOUT THE AUTHOR(S)

Terry Sejnowski is an investigator with the Howard Hughes Medical Institute and is Francis Crick Professor at the Salk Institute for Biological Studies, where he directs the Computational Neurobiology Laboratory.

Tobi Delbruck is co-leader of the sensors group at the Institute of Neuroinformatics at the University of Zurich.

 MORE TO EXPLORE

Terry Sejnowski’s 2008 Wolfgang Pauli Lectures on how neurons compute and communicate: www.podcast.ethz.ch/podcast/episodes/?id=607

Neuromorphic Sensory Systems. Shih-Chii Liu and Tobi Delbruck in Current Opinion in Neurobiology, Vol. 20, No. 3, pages 288–295; June 2010. http://tinyurl.com/bot7ag8

SCIENTIFIC AMERICAN ONLINE
Watch a video about a motion-sensing video camera that uses spikes for imaging at ScientificAmerican.com/oct2012/dvs

Seven years ago, the Havasupai Indians, who live amid the turquoise waterfalls and red cliffs miles deep in the Grand Canyon, issued a “banishment order” to keep Arizona State University employees from setting foot on their reservation — an ancient punishment for what they regarded as a genetic-era betrayal.
Members of the tiny, isolated tribe had given DNA samples to university researchers starting in 1990, in the hope that they might provide genetic clues to the tribe’s devastating rate of diabetes. But they learned that their blood samples had been used to study many other things, including mental illness and theories of the tribe’s geographical origins that contradict their traditional stories.


The geneticist responsible for the research has said that she had obtained permission for wider-ranging genetic studies.


Acknowledging a desire to “remedy the wrong that was done,” the university’s Board of Regents on Tuesday agreed to pay $700,000 to 41 of the tribe’s members, return the blood samples and provide other forms of assistance to the impoverished Havasupai — a settlement that legal experts said was significant because it implied that the rights of research subjects can be violated when they are not fully informed about how their DNA might be used.
The case raised the question of whether scientists had taken advantage of a vulnerable population, and it created an image problem for a university eager to cast itself as a center for American Indian studies.


But genetics experts and civil rights advocates say it may also fuel a growing debate over researchers’ responsibility to communicate the range of personal information that can be gleaned from DNA at a time when it is being collected on an ever-greater scale for research and routine medical care.
“I’m not against scientific research,” said Carletta Tilousi, 39, a member of the Havasupai tribal council. “I just want it to be done right. They used our blood for all these studies, people got degrees and grants, and they never asked our permission.”


Researchers and institutions that receive federal funds are required to receive “informed consent” from subjects, ensuring that they understand the risks and benefits before they participate. But such protections were designed primarily for research that carried physical risks, like experimental drug trials or surgery. When it comes to mining DNA, the rules — and the risks — are murkier.


Is it necessary, for instance, to ask someone who has donated DNA for research on heart disease if that DNA can be used for Alzheimer’s or addiction research?


Many scientists say no, arguing that the potential benefit from unencumbered biomedical research trumps the value of individual control.
“Everyone wants to be open and transparent,” said Dr. David Karp, an associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, who has studied informed consent for DNA research. “The question is, how far do you have to go? Do you have to create some massive database of people’s wishes for their DNA specimens?”


The Havasupai settlement appears to be the first payment to individuals who said their DNA was misused, several legal experts said, and came after the university spent $1.7 million fighting lawsuits by tribe members.
Even as the Havasupai prepared to reclaim the 151 remaining blood samples from a university freezer this week, Therese Markow, the geneticist, defended her actions as ethical. Those judging her otherwise, she suggested, failed to understand the fundamental nature of genetic research, where progress often occurs from studies that do not appear to bear directly on a particular disease.


“I was doing good science,” Dr. Markow, now a professor at the University of California, San Diego, said in a telephone interview.
Edmond Tilousi, 56, a cousin of Carletta Tilousi and the tribe’s vice chairman, can climb the eight miles from his village on the floor of the western Grand Canyon to the rim in three hours, when he is in a rush. Horse or helicopter are the other ways out, and Mr. Tilousi is increasingly rare among the tribe’s members in his ability to make the hike. Beginning in the 1960s, an extraordinarily high incidence of Type 2 diabetes led to amputations, even among the younger members, and forced many to leave the canyon for dialysis.


In late 1989, Mr. Tilousi’s uncle Rex Tilousi approached John Martin, an Arizona State University anthropologist who had gained the tribe’s trust, to ask if he knew a doctor who could help. “I asked him, ‘How can we prevent this from spreading?’ ” the elder Mr. Tilousi recalled.
Professor Martin approached Dr. Markow. A link had recently been reported between a genetic variant and the high rate of diabetes among Pima Indians. If a similar link was found among the Havasupai, it might point to an important risk factor.


The two professors received money from the university to study diabetes in the tribe. Dr. Markow was interested in schizophrenia research as well, and in the summer of 1990, with a grant from the National Alliance for Research on Schizophrenia and Depression, she and her graduate students began collecting blood samples in Supai. Women here remember being happy to see her in those days, an athletic figure who talked to them about how to be more healthy. Working out of the health clinic in the center of the village, Dr. Markow recruited tribe members to ask others to give blood. To the Havasuapi, blood has deep spiritual meaning.


“I went and told people, if they have their blood taken, it would help them,” said Floranda Uqualla, 46, whose parents and grandparents suffered from diabetes. “And we might get a cure so that our people won’t have to leave our canyon.” Roughly 100 tribe members who gave blood from 1990 to 1994 signed a broad consent that said the research was to “study the causes of behavioral/medical disorders.”
The consent form was purposely simple, Dr. Markow said, given that English was a second language for many Havasupai, and few of the tribe’s 650 members had graduated from high school. They were always given the opportunity to ask questions, she said, and students were also instructed to explain the project and get written and verbal consent from donors.


Dr. Markow examined several genes that were thought to have medical relevance, including for schizophrenia, metabolic disorders and alcoholism, she said, but found little to pursue. The Havasupai did not, it turned out, share the gene variant linked to diabetes in the Pima.
But a few years later, a graduate student using new technology came up with a way to discern variations in the Havasupai DNA, which was stored in a university freezer, and he wrote a dissertation based on his research.
Carletta Tilousi, one of the few Havasupai to attend college, stopped by Professor Martin’s office one day in 2003, and he invited her to the student’s doctoral presentation.


Ms. Tilousi understood little of the technical aspect, but what she heard bore no resemblance to the diabetes research she had pictured when she had given her own blood sample years earlier.


“Did you have permission,” she asked during the question period, “to use Havasupai blood for your research?”
The presentation was halted. Dr. Markow and the other members of the doctoral committee asked the student to redact that chapter from his dissertation.
But months later, tribe members learned more about the research when a university investigation discovered two dozen published articles based on the blood samples that Dr. Markow had collected. One reported a high degree of inbreeding, a measure that can correspond with a higher susceptibility to disease.
Ms. Tilousi found that offensive. “We say if you do that, a close relative of yours will die,” she said.


Another article, suggesting that the tribe’s ancestors had crossed the frozen Bering Sea to arrive in North America, flew in the face of the tribe’s traditional stories that it had originated in the canyon and was assigned to be its guardian.


Listening to the investigators, Ms. Tilousi felt a surge of anger, she recalled. But in Supai, the initial reaction was more of hurt. Though some Havasupai knew already that their ancestors most likely came from Asia, “when people tell us, ‘No, this is not where you are from,’ and your own blood says so — it is confusing to us,” Rex Tilousi said. “It hurts the elders who have been telling these stories to our grandchildren.”
Others questioned whether they could have unwittingly contributed to research that could threaten the tribe’s rights to its land. “Our coming from the canyon, that is the basis of our sovereign rights,” said Edmond Tilousi, the tribe’s vice chairman.


Many members are still suffering from diabetes and say they were never told if researchers had learned anything that could help them. The classes on nutrition that Dr. Markow had sponsored with grant money have since petered out.
Ms. Uqualla, who had recruited blood donors, said she felt shamed by the news that it had been used for research that could potentially damage the tribe. “I let my people down,” she said.


The money from the settlement will be divided among the 41 tribe members. Ms. Uqualla, for one, hopes to buy a horse trailer.
But Stephen F. Hanlon, a lawyer who has represented the tribe members without charge, said the resources the university agreed to provide, including scholarships and assistance in obtaining federal funds for projects like a new health clinic, had the potential to transform the tribal village at the bottom of one of the world’s most famous natural wonders.


On Tuesday, Ms. Tilousi cried as a university official unlocked the freezer in the nondescript storage room in the Tempe campus where the blood samples had long been stored. Wearing protective glasses, gloves and a lab coat, she and a delegation of tribal members sang in Havasupai as they saw the blood that had been taken from them and from their relatives, now dead.
On the box inside the freezer was scrawled the name, “Markow.”


By AMY HARMON; NYT, april 2010