He Wants to Eliminate Inherited Diseases in Embryos. Congress Just Said No (Again).
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Biologist Shoukhrat Mitalipov is famous—and controversial--in the world of cutting-edge fertility treatments. A decade ago, he pioneered mitochondrial replacement therapy, paving the way for the world's first "three-parent" babies to be born free of a devastating inherited disease.
He sees his work toward embryo gene therapy as not only moral, but necessary.
In 2017, he shocked the world again when his group at Oregon Health and Science University became the first to repair a genetic mutation causing heart disease in dozens of human embryos. The embryos were later destroyed a part of the experiment; current policy in the U.S. prohibits such research from moving into clinical trials.
And that policy doesn't look like it's going to change anytime soon, despite recent political wavering. Last month, a House subcommittee dropped the ban that has blocked the Food and Drug Administration since 2015 from considering any clinical trials of genetically altered embryos intended to create a baby. The move raised the hopes of supporters who want to see such research move forward and angered critics who feel that the science is getting ahead of the ethics. But yesterday, a House committee decided to restore the ban on gene-edited babies after all.
As for Mitalipov, he told leapsmag that he sees his work toward embryo gene therapy as not only moral, but necessary. This interview has been edited and condensed for clarity.
What motivates you to pursue this line of research, even though it is highly controversial?
It's my expertise, I'm an embryologist. We study early development in humans -- sperm, egg, and the first five days of development -- and try to use our knowledge to treat human diseases, particularly in that early stage. This is how IVF started, as a treatment for infertility. It's a very successful cell therapy treatment, with millions of children born. [Now the idea is] to actually to use this IVF platform not as much to treat infertility, but also to treat heritable genetic diseases, because this is a very important stage when gametes from either dad or mom will transmit mutations. This is the bottleneck where we could actually interfere and repair that mutation.
Many people are hesitant to support embryo editing because of "designer babies," yet polls do show that Americans are more open to embryo editing for the purpose of disease prevention. Where should society draw a line?
Yeah, I agree with most Americans that we don't have to edit -- meaning you could make all kind of changes. Instead we do gene repair, which is a therapeutic application.
Gene repair is quite different than gene editing. It involves [focusing on] already known disease-causing mutations and how we can turn them back to normal.
Thousands of gene mutations cause human diseases, like Crohn's, for example, or mutations causing cancer, heart disease. These are well-described, well-studied cause-and-effect diseases and we need to do something about it because otherwise it's impossible to treat once the mutation is already passed to a child.
Early intervention is the best in any disease, but in genetics, "early" means you have to do it at the time of fertilization. That's when we are dealing with one copy of the mutation or maybe two, versus when you have a whole body with billions of cells in solid tissues that we cannot really access and target. So this is the most efficient way of preventing thousands and thousands of genetic diseases. I understand that we have to make sure that it's very safe, of course, and efficient as well. But at the same time, I think this is the future. We have to work toward developing these technologies.
"If we continue banning the research everywhere and not funding it, maybe 100 years will not be enough."
What's your opinion of Dr. He Jiankui and the Chinese CRISPR'ed babies?
This is a case where he was doing gene editing, not gene repair. He hasn't corrected anything, he induced a mutation to normal human genes, hoping that this would somehow confer resistance to HIV, which is still unclear.
I think such straightforward editing is unacceptable specifically for human embryos. He's approach has also never been tested in an animal model. That's why the reaction from the public and scientists was very negative, because this is the case where the doctor does this without any expertise in this area, without knowing probably much about what he is doing, and he acquired it without any oversights, which is troubling. And of course, it negatively affects the legitimate research that is going on in some labs.
What might the future of embryo gene therapy look like?
Hopefully in 10 years from now, thousands and thousands of families that know they carry germline mutations…could go through IVF and we would correct it, and they could have healthy children.
Right now, we have some tools. We cannot correct, but we can select. So what happens is the parents become pregnant and then at about three months along, we can biopsy the amniotic fluid and say, "Hey unfortunately you passed on this mutation." And that means this child, if it's born, will be affected, so we give parents a choice of terminating the pregnancy.
Or we could do it much earlier, so parents go to the IVF clinic where we retrieve about ten eggs, after stimulating a woman's ovaries. Each of them will be fertilized so we have ten embryos that develop. We have a five-day window where we can keep them in the lab. And we basically reap a few cells, we do a biopsy from each of these ten, and we say, "Hey embryo number 1 and number 4 are not mutant, but the others are."
Then we can take these two and the other eight usually will be thrown away. That's the technology that we have now. Some ethicists argue on religious grounds that we have this selection technology available, so why do we need germline gene therapy [i.e. repairing the disease-causing mutations in an embryo]?
I don't understand the moral argument there, because all the available technology is based on selective destruction of the embryo.
With [IVF gene therapy], we will take ten embryos and every embryo we'll make healthy because we can get rid of the mutations. How could embryo destruction be morally superior?
How long do you think it will take for this technology to be available to prospective parents?
It depends how many legitimate labs with expertise can get into this field and resolve all the scientific questions. If we continue banning the research everywhere and not funding it, maybe 100 years will not be enough.
So far, I think that my lab is the only one legitimately working on it. But we would like five, 10, maybe 100 labs in this country and Europe really working. Because we have scientific challenges that we need to resolve before we could say, "Hey now we know how to correct [a given mutation] and now this could be efficient, and there are no side effects or very little." And then we could say, "Okay, I think we've done everything we could in petri dishes and in animals, and now we are ready to transplant this embryo in a patient and see what happens."
"There's just no way you could sink your head into the sand and say, 'Oh, we just ban it and then hopefully everything will go away.'"
Does banning emerging technology actually work?
Banning it usually means it will leak out to a gray area where there's no regulation and many private IVF clinics will just use it while it is still premature. So I think we have to regulate the clinical testing. There's just no way you could sink your head into the sand and say, "Oh, we just ban it and then hopefully everything will go away." That's not going to happen.
If this technology does become feasible and legal in the future, do you think that more and more couples will choose IVF and gene therapy versus the natural method of rolling the dice?
As sequencing technology is becoming available, like 23andMe, more and more parents will realize what kind of mutations they carry. And if your spouse carries the same mutation on the same locus, now you have very high chance of transmitting it. Most of the time today, we find out these families carry it once they have one or two children with that condition.
Of course, parents can just do it naturally in the bedroom and have a chance of transmitting or not transmitting mutations, but hopefully eventually we can say, "Hey, because of your condition, you don't want to play this Russian Roulette. Let's just do IVF." And hopefully the government will cover that kind of treatment because right now IVF is not covered in most states. And we do this therapy and then they have a healthy child.
We have 10,000 different mutations in the human population. That means probably billions of people carry mutations. And unless they go through this gene therapy through IVF, they will keep transmitting them. And we're going to keep having millions and millions of children with diseases. We have to do something about it.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Send in the Robots: A Look into the Future of Firefighting
April in Paris stood still. Flames engulfed the beloved Notre Dame Cathedral as the world watched, horrified, in 2019. The worst looked inevitable when firefighters were forced to retreat from the out-of-control fire.
But the Paris Fire Brigade had an ace up their sleeve: Colossus, a firefighting robot. The seemingly indestructible tank-like machine ripped through the blaze with its motorized water cannon. It was able to put out flames in places that would have been deadly for firefighters.
Firefighting is entering a new era, driven by necessity. Conventional methods of managing fires have been no match for the fiercer, more expansive fires being triggered by climate change, urban sprawl, and susceptible wooded areas.
Robots have been a game-changer. Inspired by Paris, the Los Angeles Fire Department (LAFD) was the first in the U.S. to deploy a firefighting robot in 2021, the Thermite Robotics System 3 – RS3, for short.
RS3 is a 3,500-pound turbine on a crawler—the size of a Smart car—with a 36.8 horsepower engine that can go for 20 hours without refueling. It can plow through hazardous terrain, move cars from its path, and pull an 8,000-pound object from a fire.
All that while spurting 2,500 gallons of water per minute with a rear exhaust fan clearing the smoke. At a recent trade show, RS3 was billed as equivalent to 10 firefighters. The Los Angeles Times referred to it as “a droid on steroids.”
Robots such as the Thermite RS3 can plow through hazardous terrain and pull an 8,000-pound object from a fire.
Los Angeles Fire Department
The advantage of the robot is obvious. Operated remotely from a distance, it greatly reduces an emergency responder’s exposure to danger, says Wade White, assistant chief of the LAFD. The robot can be sent into airplane fires, nuclear reactors, hazardous areas with carcinogens (think East Palestine, Ohio), or buildings where a roof collapse is imminent.
Advances for firefighters are taking many other forms as well. Fibers have been developed that make the firefighter’s coat lighter and more protective from carcinogens. New wearable devices track firefighters’ biometrics in real time so commanders can monitor their heat stress and exertion levels. A sensor patch is in development which takes readings every four seconds to detect dangerous gases such as methane and carbon dioxide. A sonic fire extinguisher is being explored that uses low frequency soundwaves to remove oxygen from air molecules without unhealthy chemical compounds.
The demand for this technology is only increasing, especially with the recent rise in wildfires. In 2021, fires were responsible for 3,800 deaths and 14,700 injuries of civilians in this country. Last year, 68,988 wildfires burned down 7.6 million acres. Whether the next generation of firefighting can address these new challenges could depend on special cameras, robots of the aerial variety, AI and smart systems.
Fighting fire with cameras
Another key innovation for firefighters is a thermal imaging camera (TIC) that improves visibility through smoke. “At a fire, you might not see your hand in front of your face,” says White. “Using the TIC screen, you can find the door to get out safely or see a victim in the corner.” Since these cameras were introduced in the 1990s, the price has come down enough (from $10,000 or more to about $700) that every LAFD firefighter on duty has been carrying one since 2019, says White.
TICs are about the size of a cell phone. The camera can sense movement and body heat so it is ideal as a search tool for people trapped in buildings. If a firefighter has not moved in 30 seconds, the motion detector picks that up, too, and broadcasts a distress signal and directional information to others.
To enable firefighters to operate the camera hands-free, the newest TICs can attach inside a helmet. The firefighter sees the images inside their mask.
TICs also can be mounted on drones to get a bird’s-eye, 360 degree view of a disaster or scout for hot spots through the smoke. In addition, the camera can take photos to aid arson investigations or help determine the cause of a fire.
More help From above
Firefighters prefer the term “unmanned aerial systems” (UAS) to drones to differentiate them from military use.
A UAS carrying a camera can provide aerial scene monitoring and topography maps to help fire captains deploy resources more efficiently. At night, floodlights from the drone can illuminate the landscape for firefighters. They can drop off payloads of blankets, parachutes, life preservers or radio devices for stranded people to communicate, too. And like the robot, the UAS reduces risks for ground crews and helicopter pilots by limiting their contact with toxic fumes, hazardous chemicals, and explosive materials.
“The nice thing about drones is that they perform multiple missions at once,” says Sean Triplett, team lead of fire and aviation management, tools and technology at the Forest Service.
Experts predict we’ll see swarms of drones dropping water and fire retardant on burning buildings and forests in the near future.
The UAS is especially helpful during wildfires because it can track fires, get ahead of wind currents and warn firefighters of wind shifts in real time. The U.S. Forest Service also uses long endurance, solar-powered drones that can fly for up to 30 days at a time to detect early signs of wildfire. Wildfires are no longer seasonal in California – they are a year-long threat, notes Thanh Nguyen, fire captain at the Orange County Fire Authority.
In March, Nguyen’s crew deployed a drone to scope out a huge landslide following torrential rains in San Clemente, CA. Emergency responders used photos and videos from the drone to survey the evacuated area, enabling them to stay clear of ground on the hillside that was still sliding.
Improvements in drone batteries are enabling them to fly for longer with heavier payloads. Experts predict we’ll see swarms of drones dropping water and fire retardant on burning buildings and forests in the near future.
AI to the rescue
The biggest peril for a firefighter is often what they don’t see coming. Flashovers are a leading cause of firefighter deaths, for example. They occur when flammable materials in an enclosed area ignite almost instantaneously. Or dangerous backdrafts can happen when a firefighter opens a window or door; the air rushing in can ignite a fire without warning.
The Fire Fighting Technology Group at the National Institute of Standards and Technology (NIST) is developing tools and systems to predict these potentially lethal events with computer models and artificial intelligence.
Partnering with other institutions, NIST researchers developed the Flashover Prediction Neural Network (FlashNet) after looking at common house layouts and running sets of scenarios through a machine-learning model. In the lab, FlashNet was able to predict a flashover 30 seconds before it happened with 92.1% success. When ready for release, the technology will be bundled with sensors that are already installed in buildings, says Anthony Putorti, leader of the NIST group.
The NIST team also examined data from hundreds of backdrafts as a basis for a machine-learning model to predict them. In testing chambers the model predicted them correctly 70.8% of the time; accuracy increased to 82.4% when measures of backdrafts were taken in more positions at different heights in the chambers. Developers are working on how to integrate the AI into a small handheld device that can probe the air of a room through cracks around a door or through a created opening, Putorti says. This way, the air can be analyzed with the device to alert firefighters of any significant backdraft risk.
Early wildfire detection technologies based on AI are in the works, too. The Forest Service predicts the acreage burned each year during wildfires will more than triple in the next 80 years. By gathering information on historic fires, weather patterns, and topography, says White, AI can help firefighters manage wildfires before they grow out of control and create effective evacuation plans based on population data and fire patterns.
The future is connectivity
We are in our infancy with “smart firefighting,” says Casey Grant, executive director emeritus of the Fire Protection Research Foundation. Grant foresees a new era of cyber-physical systems for firefighters—a massive integration of wireless networks, advanced sensors, 3D simulations, and cloud services. To enhance teamwork, the system will connect all branches of emergency responders—fire, emergency medical services, law enforcement.
FirstNet (First Responder Network Authority) now provides a nationwide high-speed broadband network with 5G capabilities for first responders through a terrestrial cell network. Battling wildfires, however, the Forest Service needed an alternative because they don’t always have access to a power source. In 2022, they contracted with Aerostar for a high altitude balloon (60,000 feet up) that can extend cell phone power and LTE. “It puts a bubble of connectivity over the fire to hook in the internet,” Triplett explains.
A high altitude balloon, 60,000 feet high, can extend cell phone power and LTE, putting a "bubble" of internet connectivity over fires.
Courtesy of USDA Forest Service
Advances in harvesting, processing and delivering data will improve safety and decision-making for firefighters, Grant sums up. Smart systems may eventually calculate fire flow paths and make recommendations about the best ways to navigate specific fire conditions. NIST’s plan to combine FlashNet with sensors is one example.
The biggest challenge is developing firefighting technology that can work across multiple channels—federal, state, local and tribal systems as well as for fire, police and other emergency services— in any location, says Triplett. “When there’s a wildfire, there are no political boundaries,” he says. “All hands are on deck.”
New device can diagnose concussions using AI
For a long time after Mary Smith hit her head, she was not able to function. Test after test came back normal, so her doctors ruled out the concussion, but she knew something was wrong. Finally, when she took a test with a novel EyeBOX device, recently approved by the FDA, she learned she indeed had been dealing with the aftermath of a concussion.
“I felt like even my husband and doctors thought I was faking it or crazy,” recalls Smith, who preferred not to disclose her real name. “When I took the EyeBOX test it showed that my eyes were not moving together and my BOX score was abnormal.” To her diagnosticians, scientists at the Minneapolis-based company Oculogica who developed the EyeBOX, these markers were concussion signs. “I cried knowing that finally someone could figure out what was wrong with me and help me get better,” she says.
Concussion affects around 42 million people worldwide. While it’s increasingly common in the news because of sports injuries, anything that causes damage to the head, from a fall to a car accident, can result in a concussion. The sudden blow or jolt can disrupt the normal way the brain works. In the immediate aftermath, people may suffer from headaches, lose consciousness and experience dizziness, confusion and vomiting. Some recover but others have side effects that can last for years, particularly affecting memory and concentration.
There is no simple standard-of-care test to confirm a concussion or rule it out. Neither do they appear on MRI and CT scans. Instead, medical professionals use more indirect approaches that test symptoms of concussions, such as assessments of patients’ learning and memory skills, ability to concentrate and problem solving. They also look at balance and coordination. Most tests are in the form of questionnaires or symptom checklists. Consequently, they have limitations, can be biased and may miss a concussion or produce a false positive. Some people suspected of having a concussion may ordinarily have difficulties with literary and problem-solving tests because of language challenges or education levels.
Another problem with current tests is that patients, particularly soldiers who want to return to combat and athletes who would like to keep competing, could try and hide their symptoms to avoid being diagnosed with a brain injury. Trauma physicians who work with concussion patients have the need for a tool that is more objective and consistent.
“This type of assessment doesn’t rely on the patient's education level, willingness to follow instructions or cooperation. You can’t game this.” -- Uzma Samadani, founder of Oculogica
“The importance of having an objective measurement tool for the diagnosis of concussion is of great importance,” says Douglas Powell, associate professor of biomechanics at the University of Memphis, with research interests in sports injury and concussion. “While there are a number of promising systems or metrics, we have yet to develop a system that is portable, accessible and objective for use on the sideline and in the clinic. The EyeBOX may be able to address these issues, though time will be the ultimate test of performance.”
The EyeBOX as a window inside the brain
Using eye movements to diagnose a concussion has emerged as a promising technique since around 2010. Oculogica combined eye movements with AI to develop the EyeBOX to develop an unbiased objective diagnostic tool.
“What’s so great about this type of assessment is it doesn’t rely on the patient's education level, willingness to follow instructions or cooperation,” says Uzma Samadani, a neurosurgeon and brain injury researcher at the University of Minnesota, who founded Oculogica. “You can’t game this. It assesses functions that are prompted by your brain.”
In 2010, Samadani was working on a clinical trial to improve the outcome of brain injuries. The team needed some way to measure if seriously brain injured patients were improving. One thing patients could do was watch TV. So Samadani designed and patented an AI-based algorithm that tracks the relationship between eye movement and concussion.
The EyeBOX test requires patients to watch movie or music clips for 220 seconds. An eye tracking camera records subconscious eye movements, tracking eye positions 500 times per seconds as patients watch the video. It collects over 100,000 data points. The device then uses AI to assess whether there’s any disruptions from the normal way the eyes move.
Cranial nerves are responsible for transmitting information between the brain and the body. Many are involved in eye movement. Pressure caused by a concussion can affect how these nerves work. So tracking how the eyes move can indicate if there’s anything wrong with the cranial nerves and where the problem lies.
If someone is healthy, their eyes should be able to focus on an object, follow movement and both eyes should be coordinated with each other. The EyeBox can detect abnormalities. For example, if a patient’s eyes are coordinated but they are not moving as they should, that indicates issues in the central brain stem, whilst only one eye moving abnormally suggests that a particular nerve section is affected.
Uzma Samadani with the EyeBOX device
Courtesy Oculogica
“The EyeBOX is a monitor for cranial nerves,” says Samadani. “Essentially it’s a form of digital neurological exam. “Several other eye-tracking techniques already exist, but they rely on subjective self-reported symptoms. Many also require a baseline, a measure of how patients reacted when they were healthy, which often isn’t available.
VOMS (Vestibular Ocular Motor Screen) is one of the most accurate diagnostic tests used in clinics in combination with other tests, but it is subjective. It involves a therapist getting patients to move their head or eyes as they focus or follow a particular object. Patients then report their symptoms.
The King-Devick test measures how fast patients can read numbers and compares it to a baseline. Since it is mainly used for athletes, the initial test is completed before the season starts. But participants can manipulate it. It also cannot be used in emergency rooms because the majority of patients wouldn’t have prior baseline tests.
Unlike these tests, EyeBOX doesn’t use a baseline and is objective because it doesn’t rely on patients’ answers. “It shows great promise,” says Thomas Wilcockson, a senior lecturer of psychology in Loughborough University, who is an expert in using eye tracking techniques in neurological disorders. “Baseline testing of eye movements is not always possible. Alternative measures of concussion currently in development, including work with VR headsets, seem to currently require it. Therefore the EyeBOX may have an advantage.”
A technology that’s still evolving
In their last clinical trial, Oculogica used the EyeBOX to test 46 patients who had concussion and 236 patients who did not. The sensitivity of the EyeBOX, or the probability of it correctly identifying the patient’s concussion, was 80.4 percent. Meanwhile, the test accurately ruled out a concussion in 66.1 percent of cases. This is known as its specificity score.
While the team is working on improving the numbers, experts who treat concussion patients find the device promising. “I strongly support their use of eye tracking for diagnostic decision making,” says Douglas Powell. “But for diagnostic tests, we would prefer at least one of the sensitivity or specificity values to be greater than 90 percent. Powell compares EyeBOX with the Buffalo Concussion Treadmill Test, which has sensitivity and specificity values of 73 and 78 percent, respectively. The VOMS also has shown greater accuracy than the EyeBOX, at least for now. Still, EyeBOX is competitive with the best diagnostic testing available for concussion and Powell hopes that its detection prowess will improve. “I anticipate that the algorithms being used by Oculogica will be under continuous revision and expect the results will improve within the next several years.”
“The color of your skin can have a huge impact in how quickly you are triaged and managed for brain injury. People of color have significantly worse outcomes after traumatic brain injury than people who are white.” -- Uzma Samadani, founder of Oculogica
Powell thinks the EyeBOX could be an important complement to other concussion assessments.
“The Oculogica product is a viable diagnostic tool that supports clinical decision making. However, concussion is an injury that can present with a wide array of symptoms, and the use of technology such as the Oculogica should always be a supplement to patient interaction.”
Ioannis Mavroudis, a consultant neurologist at Leeds Teaching Hospital, agrees that the EyeBOX has promise, but cautions that concussions are too complex to rely on the device alone. For example, not all concussions affect how eyes move. “I believe that it can definitely help, however not all concussions show changes in eye movements. I believe that if this could be combined with a cognitive assessment the results would be impressive.”
The Oculogica team submitted their clinical data for FDA approval and received it in 2018. Now, they’re working to bring the test to the commercial market and using the device clinically to help diagnose concussions for clients. They also want to look at other areas of brain health in the next few years. Samadani believes that the EyeBOX could possibly be used to detect diseases like multiple sclerosis or other neurological conditions. “It’s a completely new way of figuring out what someone’s neurological exam is and we’re only beginning to realize the potential,” says Samadani.
One of Samadani’s biggest aspirations is to help reduce inequalities in healthcare because of skin color and other factors like money or language barriers. From that perspective, the EyeBOX’s greatest potential could be in emergency rooms. It can help diagnose concussions in addition to the questionnaires, assessments and symptom checklists, currently used in the emergency departments. Unlike these more subjective tests, EyeBOX can produce an objective analysis of brain injury through AI when patients are admitted and assessed, unrelated to their socioeconomic status, education, or language abilities. Studies suggest that there are racial disparities in how patients with brain injuries are treated, such as how quickly they're assessed and get a treatment plan.
“The color of your skin can have a huge impact in how quickly you are triaged and managed for brain injury,” says Samadani. “As a result of that, people of color have significantly worse outcomes after traumatic brain injury than people who are white. The EyeBOX has the potential to reduce inequalities,” she explains.
“If you had a digital neurological tool that you could screen and triage patients on admission to the emergency department you would potentially be able to make sure that everybody got the same standard of care,” says Samadani. “My goal is to change the way brain injury is diagnosed and defined.”