Genetically Sequencing Healthy Babies Yielded Surprising Results
Today in Melrose, Massachusetts, Cora Stetson is the picture of good health, a bubbly precocious 2-year-old. But Cora has two separate mutations in the gene that produces a critical enzyme called biotinidase and her body produces only 40 percent of the normal levels of that enzyme.
In the last few years, the dream of predicting and preventing diseases through genomics, starting in childhood, is finally within reach.
That's enough to pass conventional newborn (heelstick) screening, but may not be enough for normal brain development, putting baby Cora at risk for seizures and cognitive impairment. But thanks to an experimental study in which Cora's DNA was sequenced after birth, this condition was discovered and she is being treated with a safe and inexpensive vitamin supplement.
Stories like these are beginning to emerge from the BabySeq Project, the first clinical trial in the world to systematically sequence healthy newborn infants. This trial was led by my research group with funding from the National Institutes of Health. While still controversial, it is pointing the way to a future in which adults, or even newborns, can receive comprehensive genetic analysis in order to determine their risk of future disease and enable opportunities to prevent them.
Some believe that medicine is still not ready for genomic population screening, but others feel it is long overdue. After all, the sequencing of the Human Genome Project was completed in 2003, and with this milestone, it became feasible to sequence and interpret the genome of any human being. The costs have come down dramatically since then; an entire human genome can now be sequenced for about $800, although the costs of bioinformatic and medical interpretation can add another $200 to $2000 more, depending upon the number of genes interrogated and the sophistication of the interpretive effort.
Two-year-old Cora Stetson, whose DNA sequencing after birth identified a potentially dangerous genetic mutation in time for her to receive preventive treatment.
(Photo courtesy of Robert Green)
The ability to sequence the human genome yielded extraordinary benefits in scientific discovery, disease diagnosis, and targeted cancer treatment. But the ability of genomes to detect health risks in advance, to actually predict the medical future of an individual, has been mired in controversy and slow to manifest. In particular, the oft-cited vision that healthy infants could be genetically tested at birth in order to predict and prevent the diseases they would encounter, has proven to be far tougher to implement than anyone anticipated.
But in the last few years, the dream of predicting and preventing diseases through genomics, starting in childhood, is finally within reach. Why did it take so long? And what remains to be done?
Great Expectations
Part of the problem was the unrealistic expectations that had been building for years in advance of the genomic science itself. For example, the 1997 film Gattaca portrayed a near future in which the lifetime risk of disease was readily predicted the moment an infant is born. In the fanfare that accompanied the completion of the Human Genome Project, the notion of predicting and preventing future disease in an individual became a powerful meme that was used to inspire investment and public support for genomic research long before the tools were in place to make it happen.
Another part of the problem was the success of state-mandated newborn screening programs that began in the 1960's with biochemical tests of the "heel-stick" for babies with metabolic disorders. These programs have worked beautifully, costing only a few dollars per baby and saving thousands of infants from death and severe cognitive impairment. It seemed only logical that a new technology like genome sequencing would add power and promise to such programs. But instead of embracing the notion of newborn sequencing, newborn screening laboratories have thus far rejected the entire idea as too expensive, too ambiguous, and too threatening to the comfortable constituency that they had built within the public health framework.
"What can you find when you look as deeply as possible into the medical genomes of healthy individuals?"
Creating the Evidence Base for Preventive Genomics
Despite a number of obstacles, there are researchers who are exploring how to achieve the original vision of genomic testing as a tool for disease prediction and prevention. For example, in our NIH-funded MedSeq Project, we were the first to ask the question: "What can you find when you look as deeply as possible into the medical genomes of healthy individuals?"
Most people do not understand that genetic information comes in four separate categories: 1) dominant mutations putting the individual at risk for rare conditions like familial forms of heart disease or cancer, (2) recessive mutations putting the individual's children at risk for rare conditions like cystic fibrosis or PKU, (3) variants across the genome that can be tallied to construct polygenic risk scores for common conditions like heart disease or type 2 diabetes, and (4) variants that can influence drug metabolism or predict drug side effects such as the muscle pain that occasionally occurs with statin use.
The technological and analytical challenges of our study were formidable, because we decided to systematically interrogate over 5000 disease-associated genes and report results in all four categories of genetic information directly to the primary care physicians for each of our volunteers. We enrolled 200 adults and found that everyone who was sequenced had medically relevant polygenic and pharmacogenomic results, over 90 percent carried recessive mutations that could have been important to reproduction, and an extraordinary 14.5 percent carried dominant mutations for rare genetic conditions.
A few years later we launched the BabySeq Project. In this study, we restricted the number of genes to include only those with child/adolescent onset that could benefit medically from early warning, and even so, we found 9.4 percent carried dominant mutations for rare conditions.
At first, our interpretation around the high proportion of apparently healthy individuals with dominant mutations for rare genetic conditions was simple – that these conditions had lower "penetrance" than anticipated; in other words, only a small proportion of those who carried the dominant mutation would get the disease. If this interpretation were to hold, then genetic risk information might be far less useful than we had hoped.
Suddenly the information available in the genome of even an apparently healthy individual is looking more robust, and the prospect of preventive genomics is looking feasible.
But then we circled back with each adult or infant in order to examine and test them for any possible features of the rare disease in question. When we did this, we were surprised to see that in over a quarter of those carrying such mutations, there were already subtle signs of the disease in question that had not even been suspected! Now our interpretation was different. We now believe that genetic risk may be responsible for subclinical disease in a much higher proportion of people than has ever been suspected!
Meanwhile, colleagues of ours have been demonstrating that detailed analysis of polygenic risk scores can identify individuals at high risk for common conditions like heart disease. So adding up the medically relevant results in any given genome, we start to see that you can learn your risks for a rare monogenic condition, a common polygenic condition, a bad effect from a drug you might take in the future, or for having a child with a devastating recessive condition. Suddenly the information available in the genome of even an apparently healthy individual is looking more robust, and the prospect of preventive genomics is looking feasible.
Preventive Genomics Arrives in Clinical Medicine
There is still considerable evidence to gather before we can recommend genomic screening for the entire population. For example, it is important to make sure that families who learn about such risks do not suffer harms or waste resources from excessive medical attention. And many doctors don't yet have guidance on how to use such information with their patients. But our research is convincing many people that preventive genomics is coming and that it will save lives.
In fact, we recently launched a Preventive Genomics Clinic at Brigham and Women's Hospital where information-seeking adults can obtain predictive genomic testing with the highest quality interpretation and medical context, and be coached over time in light of their disease risks toward a healthier outcome. Insurance doesn't yet cover such testing, so patients must pay out of pocket for now, but they can choose from a menu of genetic screening tests, all of which are more comprehensive than consumer-facing products. Genetic counseling is available but optional. So far, this service is for adults only, but sequencing for children will surely follow soon.
As the costs of sequencing and other Omics technologies continue to decline, we will see both responsible and irresponsible marketing of genetic testing, and we will need to guard against unscientific claims. But at the same time, we must be far more imaginative and fast moving in mainstream medicine than we have been to date in order to claim the emerging benefits of preventive genomics where it is now clear that suffering can be averted, and lives can be saved. The future has arrived if we are bold enough to grasp it.
Funding and Disclosures:
Dr. Green's research is supported by the National Institutes of Health, the Department of Defense and through donations to The Franca Sozzani Fund for Preventive Genomics. Dr. Green receives compensation for advising the following companies: AIA, Applied Therapeutics, Helix, Ohana, OptraHealth, Prudential, Verily and Veritas; and is co-founder and advisor to Genome Medical, Inc, a technology and services company providing genetics expertise to patients, providers, employers and care systems.
Facial Recognition Can Reduce Racial Profiling and False Arrests
[Editor's Note: This essay is in response to our current Big Question, which we posed to experts with different perspectives: "Do you think the use of facial recognition technology by the police or government should be banned? If so, why? If not, what limits, if any, should be placed on its use?"]
Opposing facial recognition technology has become an article of faith for civil libertarians. Many who supported the bans in cities like San Francisco and Oakland have declared the technology to be inherently racist and abusive.
The greatest danger would be to categorically oppose this technology and pretend that it will simply go away.
I have spent my career as a criminal defense attorney and a civil libertarian -- and I do not fear it. Indeed, I see it as positive so long as it is appropriately regulated and controlled.
We are living in the beginning of a biometric age, where technology uses our physical or biological characteristics for a variety of products and services. It holds great promises as well as great risks. The greatest danger, however, would be to categorically oppose this technology and pretend that it will simply go away.
This is an age driven as much by consumer as it is government demand. Living in denial may be emotionally appealing, but it will only hasten the creation of post-privacy world. If we do not address this emerging technology, movements in public will increasingly result in instant recognition and even tracking. It is the type of fish-bowl society that strips away any expectation of privacy in our interactions and associations.
The biometrics field is expanding exponentially, largely due to the popularity of consumer products using facial recognition technology (FRT) -- from the iPhone program to shopping ones that recognize customers.
But the privacy community is losing this battle because it is using the privacy rationales and doctrines forged in the earlier electronic surveillance periods. Just as generals are often accused of planning to fight the last war, civil libertarians can sometimes cling to past models despite their decreasing relevance in the current world.
I see FRT as having positive implications that are worth pursuing. When properly used, biometrics can actually enhance privacy interests and even reduce racial profiling by reducing false arrests and the warrantless "patdowns" allowed by the Supreme Court. Bans not only deny police a technology widely used by businesses, but return police to the highly flawed default of "eye balling" suspects -- a system with a considerably higher error rate than top FRT programs.
Officers are often wrong and stop a great number of suspects in the hopes of finding a wanted felon.
A study in Australia showed that passport officers who had taken photographs of subjects in ideal conditions nonetheless experienced high error rates when identifying them shortly afterward, including 14 percent false acceptance rates. Currently, officers stop suspects based on their memory from seeing a photograph days or weeks earlier. They are often wrong and stop a great number of suspects in the hopes of finding a wanted felon. The best FRT programs achieve an astonishing accuracy rate, though real-world implementation has challenges that must be addressed.
One legitimate concern raised in early studies showed higher error rates in recognitions for certain groups, particularly African American women. An MIT study finding that error rate prompted major improvements in the algorithms as well as training changes to greatly reduce the frequency of errors. The issue remains a concern, but there is nothing inherently racist in algorithms. These are a set of computer instructions that isolate and process with the parameters and conditions set by creators.
To be sure, there is room for improvement in some algorithms. Tests performed by the American Civil Liberties Union (ACLU) reportedly showed only an 80 percent accuracy rate in comparing mug shots to pictures of members of Congress when using Amazon's "Rekognition" system. It recently showed the same 80 percent rate in doing the same comparison to members of the California legislators.
However, different algorithms are available with differing levels of performance. Moreover, these products can be set with a lower discrimination level. The fact is that the top algorithms tested by the National Institute of Standards and Technology showed that their accuracy rate is greater than 99 percent.
The greatest threat of biometric technologies is to democratic values.
Assuming a top-performing algorithm is used, the result could be highly beneficial for civil liberties as opposed to the alternative of "eye balling" suspects. Consider the Boston Bombing where police declared a "containment zone" and forced families into the street with their hands in the air.
The suspect, Dzhokhar Tsarnaev, moved around Boston and was ultimately found outside the "containment zone" once authorities abandoned near martial law. He was caught on some surveillance systems but not identified. FRT can help law enforcement avoid time-consuming area searches and the questionable practice of forcing people out of their homes to physically examine them.
If we are to avoid a post-privacy world, we will have to redefine what we are trying to protect and reconceive how we hope to protect it. In my view, the greatest threat of biometric technologies is to democratic values. Authoritarian nations like China have made huge investments into FRT precisely because they know that the threat of recognition in public deters citizens from associating or interacting with protesters or dissidents. Recognition changes conduct. That chilling effect is what we have the worry about the most.
Conventional privacy doctrines do not offer much protection. The very concept of "public privacy" is treated as something of an oxymoron by courts. Public acts and associations are treated as lacking any reasonable expectation of privacy. In the same vein, the right to anonymity is not a strong avenue for protection. We are not living in an anonymous world anymore.
Consumers want products like FaceFind, which link their images with others across social media. They like "frictionless" transactions and authentications using faceprints. Despite the hyperbole in places like San Francisco, civil libertarians will not succeed in getting that cat to walk backwards.
The basis for biometric privacy protection should not be focused on anonymity, but rather obscurity. You will be increasingly subject to transparency-forcing technology, but we can legislatively mandate ways of obscuring that information. That is the objective of the Biometric Privacy Act that I have proposed in recent research. However, no such comprehensive legislation has passed through Congress.
The ability to spot fraudulent entries at airports or recognizing a felon in flight has obvious benefits for all citizens.
We also need to recognize that FRT has many beneficial uses. Biometric guns can reduce accidents and criminals' conduct. New authentications using FRT and other biometric programs could reduce identity theft.
And, yes, FRT could help protect against unnecessary police stops or false arrests. Finally, and not insignificantly, this technology could stop serious crimes, from terrorist attacks to the capturing of dangerous felons. The ability to spot fraudulent entries at airports or recognizing a felon in flight has obvious benefits for all citizens.
We can live and thrive in a biometric era. However, we will need to bring together civil libertarians with business and government experts if we are going to control this technology rather than have it control us.
[Editor's Note: Read the opposite perspective here.]
The Case for an Outright Ban on Facial Recognition Technology
[Editor's Note: This essay is in response to our current Big Question, which we posed to experts with different perspectives: "Do you think the use of facial recognition technology by the police or government should be banned? If so, why? If not, what limits, if any, should be placed on its use?"]
In a surprise appearance at the tail end of Amazon's much-hyped annual product event last month, CEO Jeff Bezos casually told reporters that his company is writing its own facial recognition legislation.
The use of computer algorithms to analyze massive databases of footage and photographs could render human privacy extinct.
It seems that when you're the wealthiest human alive, there's nothing strange about your company––the largest in the world profiting from the spread of face surveillance technology––writing the rules that govern it.
But if lawmakers and advocates fall into Silicon Valley's trap of "regulating" facial recognition and other forms of invasive biometric surveillance, that's exactly what will happen.
Industry-friendly regulations won't fix the dangers inherent in widespread use of face scanning software, whether it's deployed by governments or for commercial purposes. The use of this technology in public places and for surveillance purposes should be banned outright, and its use by private companies and individuals should be severely restricted. As artificial intelligence expert Luke Stark wrote, it's dangerous enough that it should be outlawed for "almost all practical purposes."
Like biological or nuclear weapons, facial recognition poses such a profound threat to the future of humanity and our basic rights that any potential benefits are far outweighed by the inevitable harms.
We live in cities and towns with an exponentially growing number of always-on cameras, installed in everything from cars to children's toys to Amazon's police-friendly doorbells. The use of computer algorithms to analyze massive databases of footage and photographs could render human privacy extinct. It's a world where nearly everything we do, everywhere we go, everyone we associate with, and everything we buy — or look at and even think of buying — is recorded and can be tracked and analyzed at a mass scale for unimaginably awful purposes.
Biometric tracking enables the automated and pervasive monitoring of an entire population. There's ample evidence that this type of dragnet mass data collection and analysis is not useful for public safety, but it's perfect for oppression and social control.
Law enforcement defenders of facial recognition often state that the technology simply lets them do what they would be doing anyway: compare footage or photos against mug shots, drivers licenses, or other databases, but faster. And they're not wrong. But the speed and automation enabled by artificial intelligence-powered surveillance fundamentally changes the impact of that surveillance on our society. Being able to do something exponentially faster, and using significantly less human and financial resources, alters the nature of that thing. The Fourth Amendment becomes meaningless in a world where private companies record everything we do and provide governments with easy tools to request and analyze footage from a growing, privately owned, panopticon.
Tech giants like Microsoft and Amazon insist that facial recognition will be a lucrative boon for humanity, as long as there are proper safeguards in place. This disingenuous call for regulation is straight out of the same lobbying playbook that telecom companies have used to attack net neutrality and Silicon Valley has used to scuttle meaningful data privacy legislation. Companies are calling for regulation because they want their corporate lawyers and lobbyists to help write the rules of the road, to ensure those rules are friendly to their business models. They're trying to skip the debate about what role, if any, technology this uniquely dangerous should play in a free and open society. They want to rush ahead to the discussion about how we roll it out.
We need spaces that are free from government and societal intrusion in order to advance as a civilization.
Facial recognition is spreading very quickly. But backlash is growing too. Several cities have already banned government entities, including police and schools, from using biometric surveillance. Others have local ordinances in the works, and there's state legislation brewing in Michigan, Massachusetts, Utah, and California. Meanwhile, there is growing bipartisan agreement in U.S. Congress to rein in government use of facial recognition. We've also seen significant backlash to facial recognition growing in the U.K., within the European Parliament, and in Sweden, which recently banned its use in schools following a fine under the General Data Protection Regulation (GDPR).
At least two frontrunners in the 2020 presidential campaign have backed a ban on law enforcement use of facial recognition. Many of the largest music festivals in the world responded to Fight for the Future's campaign and committed to not use facial recognition technology on music fans.
There has been widespread reporting on the fact that existing facial recognition algorithms exhibit systemic racial and gender bias, and are more likely to misidentify people with darker skin, or who are not perceived by a computer to be a white man. Critics are right to highlight this algorithmic bias. Facial recognition is being used by law enforcement in cities like Detroit right now, and the racial bias baked into that software is doing harm. It's exacerbating existing forms of racial profiling and discrimination in everything from public housing to the criminal justice system.
But the companies that make facial recognition assure us this bias is a bug, not a feature, and that they can fix it. And they might be right. Face scanning algorithms for many purposes will improve over time. But facial recognition becoming more accurate doesn't make it less of a threat to human rights. This technology is dangerous when it's broken, but at a mass scale, it's even more dangerous when it works. And it will still disproportionately harm our society's most vulnerable members.
Persistent monitoring and policing of our behavior breeds conformity, benefits tyrants, and enriches elites.
We need spaces that are free from government and societal intrusion in order to advance as a civilization. If technology makes it so that laws can be enforced 100 percent of the time, there is no room to test whether those laws are just. If the U.S. government had ubiquitous facial recognition surveillance 50 years ago when homosexuality was still criminalized, would the LGBTQ rights movement ever have formed? In a world where private spaces don't exist, would people have felt safe enough to leave the closet and gather, build community, and form a movement? Freedom from surveillance is necessary for deviation from social norms as well as to dissent from authority, without which societal progress halts.
Persistent monitoring and policing of our behavior breeds conformity, benefits tyrants, and enriches elites. Drawing a line in the sand around tech-enhanced surveillance is the fundamental fight of this generation. Lining up to get our faces scanned to participate in society doesn't just threaten our privacy, it threatens our humanity, and our ability to be ourselves.
[Editor's Note: Read the opposite perspective here.]