Most of us take our vision for granted. As a result, we take the ability to read, write, drive, and complete a multitude of other tasks for granted. However, unfortunately, sight is not so easy for everyone.
Cataracts account for about a third of these. The National Eye Institute reports that more than half of all Americans will have cataracts or will have had cataract surgery by the time they are 80, and in low- and middle-income countries, they’re the leading cause of blindness.
But now, people with vision problems may have new hope.
A Welcome Sight
Soon, cataracts may be the thing of the past, and even better, it may be possible to see a staggering three times better than 20/20 vision. Oh, and you could do it all without wearing glasses or contacts.
So what exactly does having three times better vision mean? If you can currently read a text that is 10 feet away, you would be able to read the same text from 30 feet away. What’s more, people who currently can’t see properly might be able to see a lot better than the average person.
This development comes thanks to the Ocumetics Bionic Lens. This dynamic lens essentially replaces a person’s natural eye lens. It’s placed into the eye via a saline-filled syringe, after which it unravels itself in under 10 seconds.
It may sound painful, but Dr. Garth Webb, the optometrist who invented the Ocumetics Bionic Lens, says that the procedure is identical to cataract surgery and would take just about eight minutes. He adds that people who have the specialized lenses surgically inserted would never get cataracts and that the lenses feel natural and won’t cause headaches or eyestrain.
The Bionic Lens may sound like a fairy tale (or sci-fi dream), but it’s not. It is actually the end result of years and years of research and more than a little funding — so far, the lens has taken nearly a decade to develop and has cost US$3 million.
What does it really cost to bring a drug to market?
The question is central to the debate over rising health care costs and appropriate drug pricing. President Trump campaigned on promises to lower the costs of drugs.
But numbers have been hard to come by. For years, the standard figure has been supplied by researchers at the Tufts Center for the Study of Drug Development: $2.7 billion each, in 2017 dollars.
Yet a new study looking at 10 cancer medications, among the most expensive of new drugs, has arrived at a much lower figure: a median cost of $757 million per drug. (Half cost less, and half more.)
Following approval, the 10 drugs together brought in $67 billion, the researchers also concluded — a more than sevenfold return on investment. Nine out of 10 companies made money, but revenues varied enormously. One drug had not yet earned back its development costs.
The study, published Monday in JAMA Internal Medicine, relied on company filings with the Securities and Exchange Commission to determine research and development costs.
“It seems like they have done a thoughtful and rigorous job,” said Dr. Aaron Kesselheim, director of the program on regulation, therapeutics and the law at Brigham and Women’s Hospital.
“It provides at least something of a reality check,” he added.
The figures were met with swift criticism, however, by other experts and by representatives of the biotech industry, who said that the research did not adequately take into account the costs of the many experimental drugs that fail.
“It’s a bit like saying it’s a good business to go out and buy winning lottery tickets,” Daniel Seaton, a spokesman for the Biotechnology Innovation Organization, said in an email.
Dr. Jerry Avorn, chief of the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, predicted that the paper would help fuel the debate over the prices of cancer drugs, which have soared so high “that we are getting into areas that are almost unimaginable economically,” he said.
A leukemia treatment approved recently by the Food and Drug Administration, for example, will cost $475,000 for a single treatment. It is the first of a wave of gene therapy treatments likely to carry staggering price tags.
“This is an important brick in the wall of this developing concern,” he said.
Dr. Vinay Prasad, an oncologist at Oregon Health and Science University, and Dr. Sham Mailankody, of Memorial Sloan Kettering Cancer Center, arrived at their figures after reviewing data on 10 companies that brought a cancer drug to market in the past decade.
Since the companies also were developing other drugs that did not receive approval from the F.D.A., the researchers were able to include the companies’ total spending on research and development, not just what they spent on the drugs that succeeded.
One striking example was ibrutinib, made by Pharmacyclics. It was approved in 2013 for patients with certain blood cancers who did not respond to conventional therapy.
Ibrutinib was the only drug out of four the company was developing to receive F.D.A. approval. The company’s research and development costs for their four drugs were $388 million, the company’s S.E.C. filings indicated.
Accurate figures on drug development are difficult to find and often disputed. Although it is widely cited, the Tufts study also was fiercely criticized.
One objection was that the researchers, led by Joseph A. DiMasi, did not disclose the companies’ data on development costs. The study involved ten large companies, which were not named, and 106 investigational drugs, also not named.
But Dr. DiMasi found the new study “irredeemably flawed at a fundamental level.”
“The sample consists of relatively small companies that have gotten only one drug approved, with few other drugs of any type in development,” he said. The result is “substantial selection bias,” meaning that the estimates do not accurately reflect the industry as a whole.
Ninety-five percent of cancer drugs that enter clinical trials fail, said Mr. Seaton, of the biotech industry group. “The small handful of successful drugs — those looked at by this paper — must be profitable enough to finance all of the many failures this analysis leaves unexamined.”
“When the rare event occurs that a company does win approval,” he added, “the reward must be commensurate with taking on the multiple levels of risk not seen in any other industry if drug development is to remain economically viable for prospective investors.”
Cancer drugs remain among the most expensive medications, with prices reaching the hundreds of thousands of dollars per patient.
Although the new study was small, its estimates are so much lower than previous figures, and the return on investment so great, that experts say they raise questions about whether soaring drug prices really are needed to encourage investment.
”That seems hard to swallow when they make seven times what they invested in the first four years,” Dr. Prasad said.
The new study has limitations, noted Patricia Danzon, an economist at the University of Pennsylvania’s Wharton School.
It involved just ten small biotech companies whose cancer drugs were aimed at limited groups of patients with less common diseases.
For such drugs, the F.D.A. often permits clinical trials to be very small and sometimes without control groups. Therefore development costs may have been lower for this group than for drugs that require longer and larger studies.
But, Dr. Danzon said, most new cancer drugs today are developed this way: by small companies and for small groups of patients. The companies often license or sell successful drugs to the larger companies.
The new study, she said, “is shining a light on a sector of the industry that is becoming important now.” The evidence, she added, is “irrefutable” that the cost of research and development “is small relative to the revenues.”
When it comes to drug prices, it does not matter what companies spend on research and development, Dr. Kesselheim said.
“They are based on what the market will bear.”
Correction: September 14, 2017
An earlier version of this article incorrectly identified the company that acquired a drug maker. It was AbbVie, not Janssen Biotech (which jointly develops the drug). Additionally, the article incorrectly described what AbbVie acquired. It was the company Pharmacylics, which developed the drug Imbruvica, not the drug itself.
Musk is just one of the people in Silicon Valley to take a keen interest in the “simulation hypothesis”, which argues that what we experience as reality is actually a giant computer simulation created by a more sophisticated intelligence. If it sounds a lot like The Matrix, that’s because it is.
One popular argument for the simulation hypothesis, outside of acid trips, came from Oxford University’s Nick Bostrom in 2003 (although the idea dates back as far as the 17th-century philosopher René Descartes). In a paper titled “Are You Living In a Simulation?”, Bostrom suggested that members of an advanced “posthuman” civilization with vast computing power might choose to run simulations of their ancestors in the universe.
This argument is extrapolated from observing current trends in technology, including the rise of virtual reality and efforts to map the human brain.
If we believe that there is nothing supernatural about what causes consciousness and it’s merely the product of a very complex architecture in the human brain, we’ll be able to reproduce it. “Soon there will be nothing technical standing in the way to making machines that have their own consciousness,” said Rich Terrile, a scientist at Nasa’s Jet Propulsion Laboratory.
At the same time, videogames are becoming more and more sophisticated and in the future we’ll be able to have simulations of conscious entities inside them.
“Forty years ago we had Pong – two rectangles and a dot. That’s where we were. Now 40 years later, we have photorealistic, 3D simulations with millions of people playing simultaneously and it’s getting better every year. And soon we’ll have virtual reality, we’ll have augmented reality,” said Musk. “If you assume any rate of improvement at all, then the games will become indistinguishable from reality.”
It’s a view shared by Terrile. “If one progresses at the current rate of technology a few decades into the future, very quickly we will be a society where there are artificial entities living in simulations that are much more abundant than human beings.”
If there are many more simulated minds than organic ones, then the chances of us being among the real minds starts to look more and more unlikely. As Terrile puts it: “If in the future there are more digital people living in simulated environments than there are today, then what is to say we are not part of that already?”
Reasons to believe that the universe is a simulation include the fact that it behaves mathematically and is broken up into pieces (subatomic particles) like a pixelated video game. “Even things that we think of as continuous – time, energy, space, volume – all have a finite limit to their size. If that’s the case, then our universe is both computable and finite. Those properties allow the universe to be simulated,” Terrile said.
“Quite frankly, if we are not living in a simulation, it is an extraordinarily unlikely circumstance,” he added.
So who has created this simulation? “Our future selves,” said Terrile.
Not everyone is so convinced by the hypothesis. “Is it logically possible that we are in a simulation? Yes. Are we probably in a simulation? I would say no,” said Max Tegmark, a professor of physics at MIT.
“In order to make the argument in the first place, we need to know what the fundamental laws of physics are where the simulations are being made. And if we are in a simulation then we have no clue what the laws of physics are. What I teach at MIT would be the simulated laws of physics,” he said.
Harvard theoretical physicist Lisa Randall is even more skeptical. “I don’t see that there’s really an argument for it,” she said. “There’s no real evidence.”
“It’s also a lot of hubris to think we would be what ended up being simulated.”
Terrile believes that recognizing that we are probably living in a simulation is as game-changing as Copernicus realizing that the Earth was not the center of the universe. “It was such a profound idea that it wasn’t even thought of as an assumption,” he said.
Before Copernicus, scientists had tried to explain the peculiar behaviour of the planets’ motion with complex mathematical models. “When they dropped the assumption, everything else became much simpler to understand.”
That we might be in a simulation is, Terrile argues, a simpler explanation for our existence than the idea that we are the first generation to rise up from primordial ooze and evolve into molecules, biology and eventually intelligence and self-awareness. The simulation hypothesis also accounts for peculiarities in quantum mechanics, particularly the measurement problem, whereby things only become defined when they are observed.
“For decades it’s been a problem. Scientists have bent over backwards to eliminate the idea that we need a conscious observer. Maybe the real solution is you do need a conscious entity like a conscious player of a video game,” he said.
For Tegmark, this doesn’t make sense. “We have a lot of problems in physics and we can’t blame our failure to solve them on simulation.”
How can the hypothesis be put to the test? On one hand, neuroscientists and artificial intelligence researchers can check whether it’s possible to simulate the human mind. So far, machines have proven to be good at playing chess and Go and putting captions on images. But can a machine achieve consciousness? We don’t know.
On the other hand, scientists can look for hallmarks of simulation. “Suppose someone is simulating our universe – it would be very tempting to cut corners in ways that makes the simulation cheaper to run. You could look for evidence of that in an experiment,” said Tegmark.
For Terrile, the simulation hypothesis has “beautiful and profound” implications.
First, it provides a scientific basis for some kind of afterlife or larger domain of reality above our world. “You don’t need a miracle, faith or anything special to believe it. It comes naturally out of the laws of physics,” he said.
Second, it means we will soon have the same ability to create our own simulations.
“We will have the power of mind and matter to be able to create whatever we want and occupy those worlds.”
Intranet service? Check. Autonomous motorcycle? Check. Driverless car technology? Check. Obviously the next logical project for a successful Silicon Valley engineer is to set up an AI-worshipping religious organization.
Anthony Levandowski, who is at the center of a legal battle between Uber and Google’s Waymo, has established a nonprofit religious corporation called Way of the Future, according to state filings first uncovered by Wired’s Backchannel. Way of the Future’s startling mission: “To develop and promote the realization of a Godhead based on artificial intelligence and through understanding and worship of the Godhead contribute to the betterment of society.”
Levandowski was co-founder of autonomous trucking company Otto, which Uber bought in 2016. He was fired from Uber in May amid allegations that he had stolen trade secrets from Google to develop Otto’s self-driving technology. He must be grateful for this religious fall-back project, first registered in 2015.
The Way of the Future team did not respond to requests for more information about their proposed benevolent AI overlord, but history tells us that new technologies and scientific discoveries have continually shaped religion, killing old gods and giving birth to new ones.
As author Yuval Noah Harari notes: “That is why agricultural deities were different from hunter-gatherer spirits, why factory hands and peasants fantasised about different paradises, and why the revolutionary technologies of the 21st century are far more likely to spawn unprecedented religious movements than to revive medieval creeds.”
Religions, Harari argues, must keep up with the technological advancements of the day or they become irrelevant, unable to answer or understand the quandaries facing their disciples.
“The church does a terrible job of reaching out to Silicon Valley types,” acknowledges Christopher Benek a pastor in Florida and founding chair of the Christian Transhumanist Association.
Silicon Valley, meanwhile, has sought solace in technology and has developed quasi-religious concepts including the “singularity”, the hypothesis that machines will eventually be so smart that they will outperform all human capabilities, leading to a superhuman intelligence that will be so sophisticated it will be incomprehensible to our tiny fleshy, rational brains.
For futurists like Ray Kurzweil, this means we’ll be able to upload copies of our brains to these machines, leading to digital immortality. Others like Elon Musk and Stephen Hawking warn that such systems pose an existential threat to humanity.
“With artificial intelligence we are summoning the demon,” Musk said at a conference in 2014. “In all those stories where there’s the guy with the pentagram and the holy water, it’s like – yeah, he’s sure he can control the demon. Doesn’t work out.”
Benek argues that advanced AI is compatible with Christianity – it’s just another technology that humans have created under guidance from God that can be used for good or evil.
“I totally think that AI can participate in Christ’s redemptive purposes,” he said, by ensuring it is imbued with Christian values.
“Even if people don’t buy organized religion, they can buy into ‘do unto others’.”
For transhumanist and “recovering Catholic” Zoltan Istvan, religion and science converge conceptually in the singularity.
“God, if it exists as the most powerful of all singularities, has certainly already become pure organized intelligence,” he said, referring to an intelligence that “spans the universe through subatomic manipulation of physics”.
“And perhaps, there are other forms of intelligence more complicated than that which already exist and which already permeate our entire existence. Talk about ghost in the machine,” he added.
For Istvan, an AI-based God is likely to be more rational and more attractive than current concepts (“the Bible is a sadistic book”) and, he added, “this God will actually exist and hopefully will do things for us.”
We don’t know whether Levandowski’s Godhead ties into any existing theologies or is a manmade alternative, but it’s clear that advancements in technologies including AI and bioengineering kick up the kinds of ethical and moral dilemmas that make humans seek the advice and comfort from a higher power: what will humans do once artificial intelligence outperforms us in most tasks? How will society be affected by the ability to create super-smart, athletic “designer babies” that only the rich can afford? Should a driverless car kill five pedestrians or swerve to the side to kill the owner?
If traditional religions don’t have the answer, AI – or at least the promise of AI – might be alluring.
A team of scientists at Wake Forest Institute for Regenerative Medicine and nine other institutions has engineered miniature 3D human hearts, lungs, and livers to achieve more realistic testing of how the human body responds to new drugs.
The “body-on-a-chip” project, funded by the Defense Threat Reduction Agency, aims to help reduce the estimated $2 billion cost and 90 percent failure rate that pharmaceutical companies face when developing new medications. The research is described in an open-access paper in Scientific Reports, published by Nature.
Using the same expertise they’ve employed to build new organs for patients, the researchers connected together micro-sized 3D liver, heart, and lung organs-on-a chip (or “organoids”) on a single platform to monitor their function. They selected heart and liver for the system because toxicity to these organs is a major reason for drug candidate failures and drug recalls. And lungs were selected because they’re the point of entry for toxic particles and for aerosol drugs such as asthma inhalers.
The integrated three-tissue organ-on-a-chip platform combines liver, heart, and lung organoids. (Top) Liver and cardiac modules are created by bioprinting spherical organoids using customized bioinks, resulting in 3D hydrogel constructs (upper left) that are placed into the microreactor devices. (Bottom) Lung modules are formed by creating layers of cells over porous membranes within microfluidic devices. TEER (trans-endothelial [or epithelial] electrical resistance sensors allow for monitoring tissue barrier function integrity over time. The three organoids are placed in a sealed, monitored system with a real-time camera. A nutrient-filled liquid that circulates through the system keeps the organoids alive and is used to introduce potential drug therapies into the system. (credit: Aleksander Skardal et al./Scientific Reports)
Why current drug testing fails
Drug compounds are currently screened in the lab using human cells and then tested in animals. But these methods don’t adequately replicate how drugs affect human organs. “If you screen a drug in livers only, for example, you’re never going to see a potential side effect to other organs,” said Aleks Skardal, Ph.D., assistant professor at Wake Forest Institute for Regenerative Medicine and lead author of the paper.
In many cases during testing of new drug candidates — and sometimes even after the drugs have been approved for use — drugs also have unexpected toxic effects in tissues not directly targeted by the drugs themselves, he explained. “By using a multi-tissue organ-on-a-chip system, you can hopefully identify toxic side effects early in the drug development process, which could save lives as well as millions of dollars.”
“There is an urgent need for improved systems to accurately predict the effects of drugs, chemicals and biological agents on the human body,” said Anthony Atala, M.D., director of the institute and senior researcher on the multi-institution study. “The data show a significant toxic response to the drug as well as mitigation by the treatment, accurately reflecting the responses seen in human patients.”
Advanced drug screening, personalized medicine
The scientists conducted multiple scenarios to ensure that the body-on-a-chip system mimics a multi-organ response.
For example, they introduced a drug used to treat cancer into the system. Known to cause scarring of the lungs, the drug also unexpectedly affected the system’s heart. (A control experiment using only the heart failed to show a response.) The scientists theorize that the drug caused inflammatory proteins from the lung to be circulated throughout the system. As a result, the heart increased beats and then later stopped altogether, indicating a toxic side effect.
“This was completely unexpected, but it’s the type of side effect that can be discovered with this system in the drug development pipeline,” Skardal noted.
Test of “liver on a chip” response to two drugs to demonstrate clinical relevance. Liver construct toxicity response was assessed following exposure to acetaminophen (APAP) and the clinically-used APAP countermeasure N-acetyl-L-cysteine (NAC). Liver constructs in the fluidic system (left) were treated with no drug (b), 1 mM APAP (c), and 10 mM APAP (d) — showing progressive loss of function and cell death, compared to 10 mM APAP +20 mM NAC (e), which mitigated those negative effects. The data shows both a significant cytotoxic (cell-damage) response to APAP as well as its mitigation by NAC treatment — accurately reflecting the clinical responses seen in human patients. (credit: Aleksander Skardal et al./Scientific Reports)
The scientists are now working to increase the speed of the system for large scale screening and add additional organs.
“Eventually, we expect to demonstrate the utility of a body-on-a-chip system containing many of the key functional organs in the human body,” said Atala. “This system has the potential for advanced drug screening and also to be used in personalized medicine — to help predict an individual patient’s response to treatment.”
Several patent applications comprising the technology described in the paper have been filed.
The international collaboration included researchers at Wake Forest Institute for Regenerative Medicine at the Wake Forest School of Medicine, Harvard-MIT Division of Health Sciences and Technology, Wyss Institute for Biologically Inspired Engineering at Harvard University, Biomaterials Innovation Research Center at Harvard Medical School, Bloomberg School of Public Health at Johns Hopkins University, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Brigham and Women’s Hospital, University of Konstanz, Konkuk University (Seoul), and King Abdulaziz University.
Abstract of Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform
Many drugs have progressed through preclinical and clinical trials and have been available – for years in some cases – before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a three-tissue organ-on-a-chip system, comprised of liver, heart, and lung, and highlight examples of inter-organ responses to drug administration. We observe drug responses that depend on inter-tissue interaction, illustrating the value of multiple tissue integration for in vitro study of both the efficacy of and side effects associated with candidate drugs.