The Science Sleuth Holding Fraudulent Research Accountable
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.
Introduction by Mary Inman, Whistleblower Attorney
For most people, when they see the word "whistleblower," the image that leaps to mind is a lone individual bravely stepping forward to shine a light on misconduct she has witnessed first-hand. Meryl Streep as Karen Silkwood exposing safety violations observed while working the line at the Kerr-McGee plutonium plant. Matt Damon as Mark Whitacre in The Informant!, capturing on his pocket recorder clandestine meetings between his employer and its competitors to fix the price of lysine. However, a new breed of whistleblower is emerging who isn't at the scene of the crime but instead figures it out after the fact through laborious review of publicly available information and expert analysis. Elisabeth Bik belongs to this new class of whistleblower.
"There's this delicate balance where on one hand we want to spread results really fast as scientists, but on the other hand, we know it's incomplete, it's rushed and it's not great."
Using her expertise as a microbiologist and her trained eye, Bik studies publicly available scientific papers to sniff out potential irregularities in the images that suggest research fraud, later seeking retraction of the offending paper from the journal's publisher. There's no smoking gun, no first-hand account of any kind. Just countless hours spent reviewing scores of scientific papers and Bik's skills and dedication as a science fraud sleuth.
While Bik's story may not as readily lend itself to the big screen, her work is nonetheless equally heroic. By tirelessly combing scientific papers to expose research fraud, Bik is playing a vital role in holding the scientific publishing process accountable and ensuring that misleading information does not spread unchecked. This is important work in any age, but particularly so in the time of COVID, where we can ill afford the setbacks and delays of scientists building on false science. In the present climate, where science is politicized and scientific principles are under attack, strong voices like Bik's must rise above the din to ensure the scientific information we receive, and our governments act upon, is accurate. Our health and wellbeing depend on it.
Whistleblower outsiders like Bik are challenging the traditional concept of what it means to be a whistleblower. Fortunately for us, the whistleblower community is a broad church. As with most ecosystems, we all benefit from a diversity of voices —whistleblower insiders and outsiders alike. What follows is an illuminating conversation between Bik, and Ivan Oransky, the co-founder of Retraction Watch, an influential blog that reports on retractions of scientific papers and related topics. (Conversation facilitated by LeapsMag Editor-in-Chief Kira Peikoff)
Elisabeth Bik and Ivan Oransky.
(Photo credits Michel & Co Photography, San Jose, CA and Elizabeth Solaka)
Ivan
I'd like to hear your thoughts, Elisabeth, on an L.A. Times story, which was picking up a preprint about mutations and the novel coronavirus, alleging that the virus is mutating to become more infectious – even though this conclusion wasn't actually warranted.
Elisabeth
A lot of the news around it is picking up on one particular side of the story that is maybe not that much exaggerated by the scientists. I don't think this paper really showed that the mutations were causing the virus to be more virulent. Some of these viruses continuously mutate and mutate and mutate, and that doesn't necessarily make a strain more virulent. I think in many cases, a lot of people want to read something in a paper that is not actually there.
Ivan
The tone level, everything that's being published now, it's problematic. It's being rushed, here it wasn't even peer-reviewed. But even when they are peer-reviewed, they're being peer-reviewed by people who often aren't really an expert in that particular area.
Elisabeth
That's right.
Ivan
To me, it's all problematic. At the same time, it's all really good that it's all getting out there. I think that five or 10 years ago, or if we weren't in a pandemic, maybe that paper wouldn't have appeared at all. It would have maybe been submitted to a top-ranked journal and not have been accepted, or maybe it would have been improved during peer review and bounced down the ladder a bit to a lower-level journal.
Yet, now, because it's about coronavirus, it's in a major newspaper and, in fact, it's getting critiqued immediately.
Maybe it's too Pollyanna-ish, but I actually think that quick uploading is a good thing. The fear people have about preprint servers is based on this idea that the peer-reviewed literature is perfect. Once it is in a peer-reviewed journal, they think it must have gone through this incredible process. You're laughing because-
Elisabeth
I am laughing.
Ivan
You know it's not true.
Elisabeth
Yes, we both know that. I agree and I think in this particular situation, a pandemic that is unlike something our generation has seen before, there is a great, great need for fast dissemination of science.
If you have new findings, it is great that there is a thing called a preprint server where scientists can quickly share their results, with, of course, the caveat that it's not peer-reviewed yet.
It's unlike the traditional way of publishing papers, which can take months or years. Preprint publishing is a very fast way of spreading your results in a good way so that is what the world needs right now.
On the other hand, of course, there's the caveat that these are brand new results and a good scientist usually thinks about their results to really interpret it well. You have to look at it from all sides and I think with the rushed publication of preprint papers, there is no such thing as carefully thinking about what results might mean.
So there's this delicate balance where on one hand we want to spread results really fast as scientists, but on the other hand, we know it's incomplete, it's rushed and it's not great. This might be hard for the general audience to understand.
Ivan
I still think the benefits of that dissemination are more positive than negative.
Elisabeth
Right. But there's also so many papers that come out now on preprint servers and most of them are not that great, but there are some really good studies in there. It's hard to find those nuggets of really great papers. There's just a lot of papers that come out now.
Ivan
Well, you've made more than a habit of finding problems in papers. These are mostly, of course, until now published papers that you examined, but what is this time like for you? How is it different?
Elisabeth
It's different because in the beginning I looked at several COVID-19-related papers that came out and wrote some critiques about it. I did experience a lot of backlash because of that. So I felt I had to take a break from social media and from writing about COVID-19.
I focused a little bit more on other work because I just felt that a lot of these papers on COVID-19 became so politically divisive that if you tried to be a scientist and think critically about a paper, you were actually assigned to a particular political party or to be against other political parties. It's hard for me to be sucked into the political discussion and to the way that our society now is so completely divided into two camps that seem to be not listening to each other.
Ivan
I was curious about that because I've followed your work for a number of years, as you know, and certainly you have had critics before. I'm thinking of the case in China that you uncovered, the leading figure in the Chinese Academy who was really a powerful political figure in addition to being a scientist.
Elisabeth
So that was a case in which I found a couple of papers at first from a particular group in China, and I was just posting on a website called PubPeer, where you can post comments, concerns about papers. And in this case, these were image duplication issues, which is my specialty.
I did not realize that the group I was looking at at that moment was led by one of the highest ranked scientists in China. If I had known that, I would probably not have posted that under my full name, but under a pseudonym. Since I had already posted, some people were starting to send me direct messages on Twitter like, "OMG, the guy you're posting about now is the top scientist in China so you're going to have a lot of backlash."
Then I decided I'll just continue doing this. I found a total of around 50 papers from this group and posted all of them on PubPeer. That story quickly became a very popular story in China: number two on Sina Weibo, a social media site in China.
I was surprised it wasn't suppressed by the Chinese government, it was actually allowed by journalists that were writing about it, and I didn't experience a lot of backlash because of that.
Actually the Chinese doctor wrote me an email saying that he appreciated my feedback and that he would look into these cases. He sent a very polite email so I sent him back that I appreciated that he would look into these cases and left it there.
Ivan
There are certain subjects that I know when we write about them in Retraction Watch, they have tended in the past to really draw a lot of ire. I'm thinking anything about vaccines and autism, anything about climate change, stem cell research.
For a while that last subject has sort of died down. But now it's become a highly politically charged atmosphere. Do you feel that this pandemic has raised the profile of people such as yourself who we refer to as scientific sleuths, people who look critically and analytically at new research?
Elisabeth
Yeah, some people. But I'm also worried that some people who are great scientists and have shown a lot of critical thinking are being attacked because of that. If you just look at what happened to Dr. Fauci, I think that's a prime example. Where somebody who actually is very knowledgeable and very cautious of new science has not been widely accepted as a great leader, in our country at least. It's sad to see that. I'm just worried how long he will be at his position, to be honest.
Ivan
We noticed a big uptick in our traffic in the last few days to Retraction Watch and it turns out it was because someone we wrote about a number of years ago has really hopped on the bandwagon to try and discredit and even try to have Dr. Fauci fired.
It's one of these reminders that the way people think about scientists has, in many cases, far more to do with their own history or their own perspective going in than with any reality or anything about the science. It's pretty disturbing, but it's not a new thing. This has been happening for a while.
You can go back and read sociologists of science from 50-60 years ago and see the same thing, but I just don't think that it's in the same way that it is now, maybe in part because of social media.
Elisabeth
I've been personally very critical about several studies, but this is the first time I've experienced being attacked by trolls and having some nasty websites written about me. It is very disturbing to read.
"I don't think that something that's been peer-reviewed is perfect and something that hasn't been peer reviewed, you should never bother reading it."
Ivan
It is. Yet you have been a fearless and vocal critic of some very high-profile papers, like the infamous French study about hydroxychloroquine.
Elisabeth
Right, the paper that came out was immediately tweeted by the President of the United States. At first I thought it was great that our President tweeted about science! I thought that was a major breakthrough. I took a look at this paper.
It had just come out that day, I believe. The first thing I noticed is that it was accepted within 24 hours of being submitted to the journal. It was actually published in a journal where one of the authors is the editor-in-chief, which is a huge conflict of interest, but it happens.
But in this particular case, there were also a lot of flaws with the study and that, I think, should have been caught during peer review. The paper was first published on a preprint server and then within 24 hours or so it was published in that paper, supposedly after peer review.
There were very few changes between the preprint version and the peer review paper. There were just a couple of extra lines, extra sentences added here and there, but it wasn't really, I think, critically looked at. Because there were a lot of things that I thought were flaws.
Just to go over a couple of them. This paper showed supposedly that people who were treated with hydroxychloroquine and azithromycin were doing much better by clearing their virus much faster than people who were not treated with these drugs.
But if you look carefully at the paper there were a couple of people who were left out of the study. So they were treated with hydroxychloroquine, but they were not shown in the end results of the paper. All six people who were treated with the drug combination were clearing the virus within six days, but there were a couple of others who were left out of the study. They also started the drug combination, but they stopped taking the drugs for several reasons and three of them were admitted to the intensive care, one died, one had some side effects and one apparently walked out of the hospital.
They were left out of the study but they were actually not doing very well with the drug combination. It's not very good science if you leave out people who don't do very well with your drug combination in your study. That was one of my biggest critiques of the paper.
Ivan
What struck us about that case was, in addition to what you, of course, mentioned, the fact that Trump tweeted it and was talking about hydroxychloroquine, was that it seemed to be a perfect example of, "well, it was in a peer review journal." Yeah, it was a preprint first, but, well, it's a peer review journal. And yet, as you point out, when you look at the history of the paper, it was accepted in 24 hours.
If you talk to most scientists, the actual act of a peer review, once you sit down to do it and can concentrate, a good one takes, again, these are averages, but four hours, a half a day is not unreasonable. So you had to find three people who could suddenly review this paper. As you pointed out, it was in a journal where one of the authors was editor.
Then some strange things also happened, right? The society that actually publishes the journal, they came out with a statement saying this wasn't up to our standards, which is odd. Then Elsevier came in, they're the ones who are actually contracted to publish the journal for the society. They said, basically, "Oh, we're going to look into this now too."
It just makes you wonder what happened before the paper was actually published. All the people who were supposed to have been involved in doing the peer review or checking on it are clearly very distraught about what actually happened. It's that scene from Casablanca, "I'm shocked, shocked there's gambling going on here." And then, "Your winnings, sir."
Elisabeth
Yes.
Ivan
And I don't actually blame the public, I don't blame reporters for getting a bit confused about what it all means and what they should trust. I don't think trust is a binary any more than anything else is a binary. I don't think that something that's been peer-reviewed is perfect and something that hasn't been peer reviewed, you should never bother reading it. I think everything is much more gray.
Yet we've turned things into a binary. Even if you go back before coronavirus, coffee is good for you, coffee is bad for you, red wine, chocolate, all the rest of it. A lot of that is because of this sort of binary construct of the world for journalists, frankly, for scientists that need to get their next grants. And certainly for the general public, they want answers.
On the one hand, if I had to choose what group of experts, or what field of human endeavor would I trust with finding the answer to a pandemic like this, or to any crisis, it would absolutely be scientists. Hands down. This is coming from someone who writes about scientific fraud.
But on the other hand, that means that if scientists aren't clear about what they don't know and about the nuances and about what the scientific method actually allows us to do and learn, that just sets them up for failure. It sets people like Dr. Fauci up for failure.
Elisabeth
Right.
Ivan
It sets up any public health official who has a discussion about models. There's a famous saying: "All models are wrong, but some are useful."
Just because the projections change, it's not proof of wrongness, it's not proof that the model is fatally flawed. In fact, I'd be really concerned if the projections didn't change based on new information. I would love it if this whole episode did lead to a better understanding of the scientific process and how scientific publishing fits into that — and doesn't fit into it.
Elisabeth
Yes, I'm with you. I'm very worried that the general audience's perspective is based on maybe watching too many movies where the scientist comes up with a conclusion one hour into the movie when everything is about to fail. Like that scene in Contagion where somebody injects, I think, eight monkeys, and one of the monkeys survives and boom we have the vaccine. That's not really how science works. Everything takes many, many years and many, many applications where usually your first ideas and your first hypothesis turn out to be completely wrong.
Then you go back to the drawing board, you develop another hypothesis and this is a very reiterative process that usually takes years. Most of the people who watch the movie might have a very wrong idea and wrong expectations about how science works. We're living in the movie Contagion and by September, we'll all be vaccinated and we can go on and live our lives. But that's not what is going to happen. It's going to take much, much longer and we're going to have to change the models every time and change our expectations. Just because we don't know all the numbers and all the facts yet.
Ivan
Generally it takes a fairly long time to change medical practice. A lot of times people see that as a bad thing. What I think that ignores, or at least doesn't take into as much account as I would, is that you don't want doctors and other health care professionals to turn on a dime and suddenly switch. Unless, of course, it turns out there was no evidence for what you were looking at.
It's a complicated situation.
Everybody wants scientists to be engineers, right?
Elisabeth
Right.
Ivan
I'm not saying engineering isn't scientific, nor am I saying that science is just completely whimsical, but there's a different process. It's a different way of looking at things and you can't just throw all the data into a big supercomputer, which is what I think a lot of people seem to want us to do, and then the obvious answer will come out on the other side.
Elisabeth
No. It's true and a lot of engineers suddenly feel their inherent need to solve this as a problem. They're not scientists and it's not building a bridge over a big river. But we're dealing with something that is very hard to solve because we don't understand the problem yet. I think scientists are usually first analyzing the problem and trying to understand what the problem actually is before you can even think about a solution.
Ivan
I think we're still at the understanding the problem phase.
Elisabeth
Exactly. And going back to the French group paper, that promised such a result and that was interpreted as such by a lot of people including presidents, but it's a very rare thing to find a medication that will have a 100% curation rate. That's something that I wish the people would understand better. We all want that to happen, but it's very unlikely and very unprecedented in the best of times.
Ivan
I would second that and also say that the world needs to better value the work that people like Elisabeth and others are doing. Because we're not going to get to a better answer if we're not rigorous about scrutinizing the literature and scrutinizing the methodology and scrutinizing the results.
"I quit my job to be able to do this work."
It's a relatively new phenomenon that you're able to do this at any scale at all, and even now it's at a very small scale. Elisabeth mentioned PubPeer and I'm a big fan — also full disclosure, I'm on their board of directors as a volunteer — it's a very powerful engine for readers and journal editors and other scientists to discuss issues.
And Elisabeth has used it really, really well. I think we need to start giving credit to people like that. And, also creating incentives for that kind of work in a way that science hasn't yet.
Elisabeth
Yeah. I quit my job to be able to do this work. It's really hard to combine it with a job either in academia or industry because we're looking for or criticizing papers and it's hard when you are still employed to do that.
I try to make it about the papers and do it in a polite way, but still it's a very hard job to do if you have a daytime job and a position and a career to worry about. Because if you're critical of other academics, that could actually mean the end of your career and that's sad. They should be more open to polite criticism.
Ivan
And for the general public, if you're reading a newspaper story or something online about a single study and it doesn't mention any other studies that have said the same thing or similar, or frankly, if it doesn't say anything about any studies that contradicted it, that's probably also telling you something.
Say you're looking at a huge painting of a shoreline, a beach, and a forest. Any single study is just a one-centimeter-by-one-centimeter square of any part of that canvas. If you just look at that, you would either think it was a painting of the sea, of a beach, or of the forest. It's actually all three of those things.
We just need to be patient, and that's very challenging to us as human beings, but we need to take the time to look at the whole picture.
DISCLAIMER: Neither Elisabeth Bik nor Ivan Oransky was compensated for participation in The Pandemic Issue. While the magazine's editors suggested broad topics for discussion, consistent with Bik's and Oransky's work, neither they nor the magazine's underwriters had any influence on their conversation.
[Editor's Note: This article was originally published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online.]
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.
Five Memorable Animals Who Expanded the Scientific Frontier
Untold numbers of animals have contributed to science, in ways big and small. Studying cows and cowpox helped English doctor Edward Jenner create a smallpox vaccine; Ivan Pavlov's experiments on dogs' reactions to external stimuli heavily influenced modern behavioral psychology.
We have these five animals to thank for some of our most important scientific advancements, from space travel to better organ replacement options.
Scientists still work with rats, rabbits, and other mammals to test cosmetics and pharmaceuticals and to conduct infectious disease research. Most of these animals remain nameless and unknown to the public, but over the years, certain individuals have had an outsize effect. We have these five animals to thank for some of our most important scientific advancements, from space travel to better organ replacement options.
1) LAIKA THE DOG
Laika was the first living creature ever to orbit the Earth. In October 1957, the Soviet Sputnik I ship had made history as the first man-made object sent into Earth's orbit; Premier Nikita Khrushchev was keen to gain another Space Race victory by sending up a canine cosmonaut.
Laika ("barker" in Russian), was a stray dog, reportedly a husky-spitz mix, recruited among several other female strays for the trip. Although the scientists put extensive work into preparing Laika and the other canine finalists—evaluating their reactions to air-pressure variations, training them to adapt to pelvic sanitation devices meant to contain waste, and eventually having them live in pressurized capsules for weeks—there was no expectation that the dog would return to Earth, and only one meal's worth of food was sent up with her.
Laika the dog, with a mockup of her space capsule.
Sputnik II, six times heavier than its predecessor, launched on November 3, 1957. Soviet broadcasts reported that Laika, fitted out with surgically implanted devices to monitor her heart rate, blood pressure, and breathing rates, survived until November 12; the spacecraft stayed in orbit for five more months, burning up when it re-entered the atmosphere.
At the time, the Sputnik II team reassured the world that Laika had died painlessly of oxygen deprivation. It was only decades later, in the 1990s, that Oleg Gazenko—one of the scientists and dog trainers assigned to the mission—revealed that Laika had died 5 to 7 hours after launch from a combination of heat and stress. The capsule had overheated, probably as a result of the rushed preparation; after the fourth orbit, the temperature inside Sputnik was over 90 degrees, and it's doubtful she could have survived much past that. "The more time passes, the more I'm sorry about it. We shouldn't have done it," Gazenko said. "We did not learn enough from the mission to justify the death of the dog."
Yet even the four or five orbits that Laika did complete were enough to spur scientists to press on in the effort to send a human into space.
2) HAM THE CHIMP
Four years after Laika's ill-fated flight, a chimpanzee named Ham entered suborbital flight in the American Project Mercury MR-2 mission on January 31, 1961, becoming the first hominid in space—and unlike Laika, he returned to Earth, alive, after a 16-minute flight.
Even though Ham's flight was not destined for orbit, the spacecraft and booster used on his trip were the same combination intended for the first (human) American's trip later that year. If he came back unharmed, NASA's medical team would be prepared to okay astronaut Alan Shepard's flight.
Ham receives his well-deserved apple.
For approximately 18 months before liftoff, Ham was trained to perform simple tasks, like pushing levers, in response to visual and auditory cues. (If he failed, he received an electric shock; correct performance earned him a treat. Pavlov would have been pleased.)
At 37 pounds, Ham was also the heaviest animal to ever make it to space. His vital signs and movements were monitored from Earth, and after a light electric shock from the ground team reminded him of his tasks, he performed his lever-pushing just a bit slower than he had on Earth, verifying that motion would not be seriously impaired in space.
Less than three months after Ham returned to Earth, on April 12, 1961, Soviet cosmonaut Yuri Gagarin became the first human to complete an orbital flight; Shepard was close behind, successfully crewing the MR-3 mission on May 5. For his part, Ham "retired" to the National Zoo in Washington D.C. for 17 years, before being transferred to the North Carolina Zoological Park; he died of liver failure in 1983 at age 26. His grave is at the International Space Hall of Fame in New Mexico.
3) KOKO THE GORILLA
A western lowland gorilla born at the San Francisco Zoo, Hanabi-ko, or "Koko," became famous in the 1970s for her cognitive and communicative abilities. Psychologist Francine "Penny" Patterson, then a doctoral student at Stanford, chose Koko to work on a language research project, teaching her American Sign Language; by age four, Koko demonstrated the ability both to make up new words and to combine known words to express herself creatively, as opposed to simply mimicking her trainer.
Koko and Penny compare notes.
Koko's work with Patterson reflected levels of cognition that were higher than non-human primates had previously been thought to have; by the end of her life, her language skills were roughly equivalent to a young child's, with a vocabulary of around 1,000 signs and the ability to understand 2,000 words of spoken English.
An especially impactful study in 2012 showed that Koko had learned to play the recorder, revealing an ability for voluntary breath control that scientists had previously thought was linked closely to speech and could only be developed by humans. Barbara J. King, a biological anthropologist, suggested that Koko's immersion in a human environment may have helped her develop such a skill, and that it might be misleading to consider similar abilities "innate" or lacking in either humans or non-human primates.
Koko's displays of emotions also fascinated the public, especially those that seemed to closely mirror humans': she cared for pet kittens; appeared on Mr. Rogers' Neighborhood and untied the host's shoes for him; acted playfully with Robin Williams during a visit from him, and later expressed grief when told about the comedian's death. Koko died in her sleep in June 2018, at age 46. Patterson continues to run The Gorilla Foundation, which is dedicated to using inter-species communication to motivate conservation efforts.
4) DOLLY THE SHEEP
Dolly—named after country singer Dolly Parton—was the first mammal ever to be cloned from an adult somatic cell, using the process of nuclear transfer. She was born in 1996 as part of research by scientists Keith Campbell and Ian Wilmut of the University of Edinburgh.
Dolly the cloned sheep.
By taking a donor cell from an adult sheep's mammary gland, using it to replace the cell nucleus of an unfertilized, developing egg cell, and then bringing the resultant embryo to term, Campbell and Wilmut proved that even a mature cell (one that had developed to perform mammary gland functions) could revert to an embryonic state and go on to develop into any and all parts of a mammal.
Although cloned livestock are legal in the U.S.—the FDA approved the practice in 2008, after determining that there was no difference between the meat and milk of cattle, pigs, and goats—Dolly has had an even bigger impact on stem cell research. The successful test of nuclear transfer proved that it was possible to change a cell's gene expression by changing its nucleus.
Japanese stem cell biologist Shinya Yamanaka, inspired by the birth of Dolly, won the Nobel Prize in 2012 for his adaptation of the technique. He developed induced pluripotent stem cells (iPS cells) by chemically reverting mature cells back to an embryonic-like blank state that is highly desirable for disease research and treatment. This technique allows researchers to work with such stem cells without the ethically charged complication of having to destroy a human embryo in the process.
5) LAIKA THE PIG
Named in honor of the dog who made it to space, the second science-famous Laika was a genetically engineered pig born in China in 2015 as a result of gene editing carried out by Cambridge, MA startup eGenesis and collaborators.* eGenesis aims to create pigs whose organs—hearts, kidneys, lungs, and more—are safe to transplant into people.
Laika the gene-edited pig.
Using animal organs in humans (xenotransplantation) is tricky: the immune system is very good at recognizing interlopers, and the human body can start to reject an organ from another species in as little as five minutes. But pigs are otherwise exceptionally good potential donors for humans: their organs' sizes and functions are very similar, and their quick gestation and maturation make them attractive from an efficiency standpoint, given that twenty Americans die every day waiting for organ donors.
Perhaps unsurprisingly, Dolly the sheep helped move xenotransplantation forward. In the 1990s, immunologist David Sachs was able to use a similar cloning method to eliminate alpha-gal, an enzyme that is produced by most animals with immune systems, including pigs—but not humans. Since our immune systems don't recognize alpha-gal, attacks on that enzyme are a major cause of organ rejection. Sachs' experiments increased the survival time of pig organs in primates to weeks: a huge improvement, but not nearly enough for someone in need of a liver or heart.
The advent of CRISPR technology, and the ability to edit genes, has allowed another leap. In 2015, researchers at eGenesis used targeted gene-editing to eliminate the genes for porcine endogenous retroviruses from pig kidney cells. These viral elements are part of all pigs' genomes and pose a potentially high risk of infecting human cells. (After the HIV/AIDS crisis especially, there was a lot of anxiety about potentially introducing a new virus into the human population.)
The eGenesis lab used nuclear transfer to embed the edited nuclei into egg cells taken from a normal pig; and Laika was born months later—without the dangerous viral genes. eGenesis is now working to make the organs even more humanlike, with the goal of one day providing organs to every human patient in need.
*[Disclosure: In 2019, eGenesis received a series B investment from Leaps By Bayer, the funding sponsor of leapsmag. However, leapsmag is editorially independent of Bayer and is under no obligation to cover companies they invest in.]
[Correction, March 3, 2020: Laika the gene-edited pig was born in China, not Cambridge, and eGenesis is pursuing xenotransplant programs that include heart, kidney, and lung, but not skin, as originally written.]
A Surprising Breakthrough Will Allow Tiny Implants to Fix—and Even Upgrade—Your Body
Imagine it's the year 2040 and you're due for your regular health checkup. Time to schedule your next colonoscopy, Pap smear if you're a woman, and prostate screen if you're a man.
"The evolution of the biological ion transistor technology is a game changer."
But wait, you no longer need any of those, since you recently got one of the new biomed implants – a device that integrates seamlessly with body tissues, because of a watershed breakthrough that happened in the early 2020s. It's an improved biological transistor driven by electrically charged particles that move in and out of your own cells. Like insulin pumps and cardiac pacemakers, the medical implants of the future will go where they are needed, on or inside the body.
But unlike current implants, biological transistors will have a remarkable range of applications. Currently small enough to fit between a patient's hair follicles, the devices could one day enable correction of problems ranging from damaged heart muscle to failing retinas to deficiencies of hormones and enzymes.
Their usefulness raises the prospect of overcorrection to the point of human enhancement, as in the bionic parts that were imagined on the ABC television series The Six Million Dollar Man, which aired in the 1970s.
"The evolution of the biological ion transistor technology is a game changer," says Zoltan Istvan, who ran as a U.S. Presidential candidate in 2016 for the Transhumanist Party and later ran for California governor. Istvan envisions humans becoming faster, stronger, and increasingly more capable by way of technological innovations, especially in the biotechnology realm. "It's a big step forward on how we can improve and upgrade the human body."
How It Works
The new transistors are more like the soft, organic machines that biology has evolved than like traditional transistors built of semiconductors and metal, according to electric engineering expert Dion Khodagholy, one of the leaders of the team at Columbia University that developed the technology.
The key to the advance, notes Khodagholy, is that the transistors will interface seamlessly with tissue, because the electricity will be of the biological type -- transmitted via the flow of ions through liquid, rather than electrons through metal. This will boost the sensitivity of detection and decoding of biological change.
Naturally, such a paradigm change in the world of medical devices raises potential societal and ethical dilemmas.
Known as an ion-gated transistor (IGT), the new class of technology effectively melds electronics with molecules of human skin. That's the current prototype, but ultimately, biological devices will be able to go anywhere in the body. "IGT-based devices hold great promise for development of fully implantable bioelectronic devices that can address key clinical issues for patients with neuropsychiatric disease," says Khodagholy, based on the expectation that future devices could fuse with, measure, and modulate cells of the human nervous system.
Ethical Implications
Naturally, such a paradigm change in the world of medical devices raises potential societal and ethical dilemmas, starting with who receives the new technology and who pays for it. But, according clinical ethicist and health care attorney David Hoffman, we can gain insight from past experience, such as how society reacted to the invention of kidney dialysis in the mid 20th century.
"Kidney dialysis has been federally funded for all these decades, largely because the who-gets-the-technology question was an issue when the technology entered clinical medicine," says Hoffman, who teaches bioethics at Columbia's College of Physicians and Surgeons as well as at the law school and medical school of Yeshiva University. Just as dialysis became a necessity for many patients, he suggests that the emerging bio-transistors may also become critical life-sustaining devices, prompting discussions about federal coverage.
But unlike dialysis, biological transistors could allow some users to become "better than well," making it more similar to medication for ADHD (attention deficit hyperactivity disorder): People who don't require it can still use it to improve their baseline normal functioning. This raises the classic question: Should society draw a line between treatment and enhancement? And who gets to decide the answer?
If it's strictly a medical use of the technology, should everyone who needs it get to use it, regardless of ability to pay, relying on federal or private insurance coverage? On the other hand, if it's used voluntarily for enhancement, should that option also be available to everyone -- but at an upfront cost?
From a transhumanist viewpoint, getting wrapped up with concerns about the evolution of devices from therapy to enhancement is not worth the trouble.
It seems safe to say that some lively debates and growing pains are on the horizon.
"Even if [the biological ion transistor] is developed only for medical devices that compensate for losses and deficiencies similar to that of a cardiac pacemaker, it will be hard to stop its eventual evolution from compensation to enhancement," says Istvan. "If you use it in a bionic eye to restore vision to the blind, how do you draw the line between replacement of normal function and provision of enhanced function? Do you pass a law placing limits on visual capabilities of a synthetic eye? Transhumanists would oppose such laws, and any restrictions in one country or another would allow another country to gain an advantage by creating their own real-life super human cyborg citizens."
In the same breath though, Istvan admits that biotechnology on a bionic scale is bound to complicate a range of international phenomena, from economic growth and military confrontations to sporting events like the Olympic Games.
The technology is already here, and it's just a matter of time before we see clinically viable, implantable devices. As for how society will react, it seems safe to say that some lively debates and growing pains are on the horizon.