Michio Kaku Talks Life on Mars, Genetic Engineering, and Immortality
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.
Dr. Michio Kaku
Today is the release of THE FUTURE OF HUMANITY, the latest book by the world-renowned physicist Dr. Michio Kaku. In it, he explores the astonishing technologies that could propel us to live on other planets and even to live forever. LeapsMag Editor-in-Chief Kira Peikoff recently chatted with Dr. Kaku about some of the ethical implications we need to consider as we hurtle toward our destiny among the stars. Our interview has been edited and condensed for clarity.
"Technology is like a double-edged sword. The question is, who wields it?"
A big part of your book discusses living on Mars, and you mention that nanotech, biotech and AI could help us do so in the next 100 years. But you also note that efforts to make the Red Planet habitable could backfire, such as using genetic engineering to produce an ideal fertilizer, which could make one life form push out all the others. How should we judge when a powerful new technology is ready to be tested?
Technology is like a double-edged sword. One side can cut against ignorance, poverty, disease. But the other side can cut against people. The question is, who wields the sword? It has to be wielded by people's interests. We have to look not at the needs of the military or corporations, but society as a whole, and we have to realize that every technology, not just the ones I mentioned in the book, has a dark side as well as a positive side.
On the positive side, you could terraform Mars using genetic engineering to create algae, plants that could thrive in the Martian atmosphere, and a self-sustaining agriculture where we could raise food crops. However, it has to be done carefully, because we don't want to have it overrun Mars, just like we have certain plants that overrun the natural environment here on Earth. So we have to do it slowly. It cannot be done all of a sudden in a crash program. We have to see what happens if we begin to terraform stretches of Martian landscape.
Elon Musk of SpaceX, who has pioneered much of these technologies, has stated that we can jumpstart terraforming Mars by detonating hydrogen bombs over the polar ice caps. Later he had to qualify that by saying that they are airbursts, not ground bursts, to minimize radiation. Other people have said, we don't know what a nuclear weapon would do. Would it destabilize Mars? Would it open cracks in the ice caps? So we have to think things through, not just make proposals. Another proposal is to use silver mirrors in space to reflect sunlight down to melt the ice caps, and that would be more environmentally friendly than using hydrogen bombs.
"Our grandkids, when they hit the age of 30, they may just decide to stop aging, and live at age 30 for many decades to come."
As far as colonizing Mars, you also talk about technologies that could potentially help us end aging, but you note that this could exacerbate overpopulation and an exodus from Earth -- the double-edged sword again. What's your personal view on whether anti-aging research should be pursued?
Anti-aging research is accelerating because of the human genome. We're now able to map the genomes of old people, compare them with the genomes of young people, and we can see where aging takes place. For example, in a car, aging takes place in the engine, because that's where we have moving parts and combustion. Where do we find that in a cell? The mitochondria, and so we do see a concentration of error build-up in the mitochondria, and we can envision one day repairing the mistakes, which could in turn increase our life span. Also we're discovering new enzymes like telomerase which allow us to stop the clock. So it's conceivable, I think not for my generation, but for the coming generations, perhaps our grandkids, when they hit the age of 30, they may just decide to stop aging, and live at age 30 for many decades to come.
The other byproduct of this of course is overpopulation. That's a social problem, but realize in places like Japan, we have the opposite problem, under-population, because the birth rate has fallen way below the replacement level, people live too long, and there's very little immigration there. Europe is next. So we have this bizarre situation where some places like Sub-Saharan Africa are still expanding, but other places we're going to see a contraction. Overall, the population will continue to rise, but it's going to slow down. Instead of this exponential curve that many people see in the media, it's going to be shaped like an "S" that rises rapidly and then seals off. The UN is now beginning to entertain the possibility that the population of the Earth may seal off sometime by the end of the century--that we'll hit a steady state.
"In the future, that composite image may be holographic, with all your videotapes, your memories, to create a near approximation of who you are, and centuries from now, you may have digital immortality."
Later in the book, you talk about achieving immortality through storing your digital consciousness, uploading your brain to a computer. Many people today find that notion bizarre or even repulsive, but you also wisely note that "what seems unethical or even immoral today might be ordinary or mundane in the future." What do you think is the key to bridging the gap between controversial breakthroughs and public acceptance?
I imagine that if someone from the Middle Ages, who is fresh from burning witches and heretics and torturing non-believers, were to wind up today in our society, they might go crazy. They might think all of society is a product of the Devil, because attitudes toward morality change. So we humans today cannot dictate what morality will be like 100 years from now. For example, test tube babies. When Louise Brown (the first test tube baby) was first born, the Catholic Church denounced it. Now, today, your wife, husband, you may be a test tube baby and we don't even blink.
There's a Silicon Valley company today that will take what is known about you on the Internet, your credit card transactions, your emails, and create a composite image of you. In the future, that composite image may be holographic, with all your videotapes, your memories, to create a near approximation of who you are, and centuries from now, you may have digital immortality—your memories, your sensations, will be recorded accurately, and an avatar will recreate it. Like for example, I wouldn't mind talking to Einstein. I wouldn't mind sitting down with the guy and having a great conversation about the universe.
And the Connectome Project, by the end of the century, will map the entire brain--that's every neuron--just like the genome project has mapped every gene. And we live with it, we don't even think twice about the fact that our genome exists. In the future, our connectome will also exist. And the connectome can reproduce your thoughts, your dreams, your sensations. We'll just live with that fact; it will be considered ordinary.
"A hundred years from now, we may want to merge with some of these technologies, rather than have to compete with robots."
Wow. In such a "post-human" era, our bodies could be replaced by robots or maintained by genetic engineering. Once these technologies become commercially available, do you think people should have the freedom to make changes or enhancements to themselves?
I think there should be laws passed at a certain point to prevent parents from going crazy trying to genetically engineer their child. Once we isolate the genes for studying, for good behavior, things like that, we may be tempted to tinker with it. I think a certain amount of tinkering is fine, but we don't want to let it get out of control. There has to be limits.
Also, we are in competition with robots of the future. A hundred years from now, robots are going to become very intelligent. Some people think they're going to take over. My attitude is that a hundred years from now, we may want to merge with some of these technologies, rather than have to compete with robots. But we're not going to look like some freaky robot because we're genetically hardwired to look good to the opposite sex, to look good to our peers. Hundreds of thousands of years ago, and hundreds of thousands of years into the future, we'll still look the same. We'll genetically modify ourselves a little bit, but we'll basically look the same.
That's an interesting point. It's amazing how fast technology is moving overall. Like at one point in the book, you mention that primates had never been cloned, but a few weeks ago, news broke that this just happened in China. Do you think we should slow down the dramatic pace of acceleration and focus on the ethical considerations, or should we still move full-steam ahead?
Well, CRISPR technology has accelerated us more than we previously thought. In the past, to tinker with genes, you had to cut and splice, and it was a lot of guesswork and trial and error. Now, you can zero in on the cutting process and streamline it, so cutting and splicing genes becomes much more accurate, and you can edit them just like you edit a book. Within the field of bioengineering, they have set up their own conferences to begin to police themselves into figuring out which domains are ethically dangerous and which areas can provide benefits for humanity, because they realize that this technology can go a little bit too fast.
"Where does truth come from? Truth comes from interaction with incorrect ideas."
You cannot recall a life form. Once a life form is created, it reproduces. That's what life does. If it reproduces outside the laboratory, it could take over. So we want to make sure that we don't have to recall a life form, like you would recall a Ford or a Chevrolet. Eventually governments may have to slow down the pace because it's moving very rapidly.
Lastly, you talk about the importance of democratic debate to resolve how controversial technology should be used. How can science-minded people bring the rest of society into these conversations, so that as much of society as possible is represented?
It's a question of where does truth come from? Truth comes from interaction with incorrect ideas--the collision of truth and untruth, rumors and fact. It doesn't come from a machine where you put in a quarter, and out comes the answer. It requires democratic debate. And that's where the Internet comes in, that's where the media comes in, that's where this interview comes in. You want to stimulate and educate the people so they know the dangers and promises of technology, and then engage with them about the moral implications, because these things are going to affect every aspect of our life in the future.
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.
Questions remain about new drug for hot flashes
In May, a new drug, Fezolinetant, was approved by the FDA to treat hot flashes associated with menopause.
Vascomotor symptoms (VMS) is the medical term for hot flashes associated with menopause. You are going to hear a lot more about it because a company has a new drug to sell. Here is what you need to know.
Menopause marks the end of a woman’s reproductive capacity. Normal hormonal production associated with that monthly cycle becomes erratic and finally ceases. For some women the transition can be relatively brief with only modest symptoms, while for others the body's “thermostat” in the brain is disrupted and they experience hot flashes and other symptoms that can disrupt daily activity. Lifestyle modification and drugs such as hormone therapy can provide some relief, but women at risk for cancer are advised not to use them and other women choose not to do so.
Fezolinetant, sold by Astellas Pharma Inc. under the product name Veozah™, was approved by the Food and Drug Administration (FDA) on May 12 to treat hot flashes associated with menopause. It is the first in a new class of drugs called neurokinin 3 receptor antagonists, which block specific neurons in the brain “thermostat” that trigger VMS. It does not appear to affect other symptoms of menopause. As with many drugs targeting a brain cell receptor, it must be taken continuously for a few days to build up a good therapeutic response, rather than working as a rescue product such as an asthma inhaler to immediately treat that condition.
Hot flashes vary greatly and naturally get better or resolve completely with time. That contributes to a placebo effect and makes it more difficult to judge the outcome of any intervention. Early this year, a meta analysis of 17 studies of drug trials for hot flashes found an unusually large placebo response in those types of studies; the placebo groups had an average of 5.44 fewer hot flashes and a 36 percent reduction in their severity.
In studies of fezolinetant, the drug recently approved by the FDA, the placebo benefit was strong and persistent. The drug group bested the placebo response to a statistically significant degree but, “If people have gone from 11 hot flashes a day to eight or seven in the placebo group and down to a couple fewer ones in the drug groups, how meaningful is that? Having six hot flashes a day is still pretty unpleasant,” says Diana Zuckerman, president of the National Center for Health Research (NCHR), a health oriented think tank.
“Is a reduction compared to placebo of 2-3 hot flashes per day, in a population of women experiencing 10-11 moderate to severe hot flashes daily, enough relief to be clinically meaningful?” Andrea LaCroix asked a commentary published in Nature Medicine. She is an epidemiologist at the University of California San Diego and a leader of the MsFlash network that has conducted a handful of NIH-funded studies on menopause.
Questions Remain
LaCroix and others have raised questions about how Astellas, the company that makes the new drug, handled missing data from patients who dropped out of the clinical trials. “The lack of detailed information about important parameters such as adherence and missing data raises concerns that the reported benefits of fezolinetant very likely overestimate those that will be observed in clinical practice," LaCroix wrote.
In response to this concern, Anna Criddle, director of global portfolio communications at Astellas, wrote in an email to Leaps.org: “…a full analysis of data, including adherence data and any impact of missing data, was submitted for assessment by [the FDA].”
The company ran the studies at more than 300 sites around the world. Curiously, none appear to have been at academic medical centers, which are known for higher quality research. Zuckerman says, "When somebody is paid to do a study, if they want to get paid to do another study by the same company, they will try to make sure that the results are the results that the company wants.”
Criddle said that Astellas picked the sites “that would allow us to reach a diverse population of women, including race and ethnicity.”
A trial of a lower dose of the drug was conducted in Asia. In March 2022, Astellas issued a press release saying it had failed to prove effectiveness. No further data has been released. Astellas still plans to submit the data, according to Criddle. Results from clinical trials funded by the U.S. goverment must be reported on clinicaltrials.gov within one year of the study's completion - a deadline that, in this case, has expired.
The measurement scale for hot flashes used in the studies, mild-moderate-severe, also came in for criticism. “It is really not good scale, there probably isn’t a broad enough range of things going on or descriptors,” says David Rind. He is chief medical officer of the Institute for Clinical and Economic Review (ICER), a nonprofit authority on new drugs. It conducted a thorough review and analysis of fezolinestant using then existing data gathered from conference abstracts, posters and presentations and included a public stakeholder meeting in December. A 252-page report was published in January, finding “considerable uncertainty about the comparative net health benefits of fezolinetant” versus hormone therapy.
Questions surrounding some of these issues might have been answered if the FDA had chosen to hold a public advisory committee meeting on fezolinetant, which it regularly does for first in class medicines. But the agency decided such a meeting was unnecessary.
Cost
There was little surprise when Astellas announced a list price for fezolinetant of $550 a month ($6000 annually) and a program of patient assistance to ease out of pocket expenses. The company had already incurred large expenses.
In 2017 Astellas purchased the company that originally developed fezolinetant for $534 million plus several hundred million in potential royalties. The drug company ran a "disease awareness” ad, Heat on the Street, hat aired during the Super Bowl in February, where 30 second ads cost about $7 million. Industry analysts have projected sales to be $1.9 billion by 2028.
ICER’s pre-approval evaluation said fezolinetant might "be considered cost-effective if priced around $2,000 annually. ... [It]will depend upon its price and whether it is considered an alternative to MHT [menopause hormone treatment] for all women or whether it will primarily be used by women who cannot or will not take MHT."
Criddle wrote that Astellas set the price based on the novelty of the science, the quality of evidence for the drug and its uniqueness compared to the rest of the market. She noted that an individual’s payment will depend on how much their insurance company decides to cover. “[W]e expect insurance coverage to increase over the course of the year and to achieve widespread coverage in the U.S. over time.”
Leaps.org wrote to and followed up with nine of the largest health insurers/providers asking basic questions about their coverage of fezolinetant. Only two responded. Jennifer Martin, the deputy chief consultant for pharmacy benefits management at the Department of Veterans Affairs, said the agency “covers all drugs from the date that they are launched.” Decisions on whether it will be included in the drug formulary and what if any copays might be required are under review.
“[Fezolinetant] will go through our standard P&T Committee [patient and treatment] review process in the next few months, including a review of available efficacy data, safety data, clinical practice guidelines, and comparison with other agents used for vasomotor symptoms of menopause," said Phil Blando, executive director of corporate communications for CVS Health.
Other insurers likely are going through a similar process to decide issues such as limiting coverage to women who are advised not to use hormones, how much copay will be required, and whether women will be required to first try other options or obtain approvals before getting a prescription.
Rind wants to see a few years of use before he prescribes fezolinetant broadly, and believes most doctors share his view. Nor will they be eager to fill out the additional paperwork required for women to participate in the Astellas patient assistance program, he added.
Safety
Astellas is marketing its drug by pointing out risks of hormone therapy, such as a recent paper in The BMJ, which noted that women who took hormones for even a short period of time had a 24 percent increased risk of dementia. While the percentage was scary, the combined number of women both on and off hormones who developed dementia was small. And it is unclear whether hormones are causing dementia or if more severe hot flashes are a marker for higher risk of developing dementia. This information is emerging only after 80 years of hundreds of millions of women using hormones.
In contrast, the label for fezolinetant prohibits “concomitant use with CYP1A2 inhibitors” and requires testing for liver and kidney function prior to initiating the drug and every three months thereafter. There is no human or animal data on use in a geriatric population, defined as 65 or older, a group that is likely to use the drug. Only a few thousand women have ever taken fezolinetant and most have used it for just a few months.
Options
A woman seeking relief from symptoms of menopause would like to see how fezolintant compares with other available treatment options. But Astellas did not conduct such a study and Andrea LaCroix says it is unlikely that anyone ever will.
ICER has come the closest, with a side-by-side analysis of evidence-based treatments and found that fezolinetant performed quite similarly and modestly as the others in providing relief from hot flashes. Some treatments also help with other symptoms of menopause, which fezolinetant does not.
There are many coping strategies that women can adopt to deal with hot flashes; one of the most common is dressing in layers (such as a sleeveless blouse with a sweater) that can be added or subtracted as conditions require. Avoiding caffeine, hot liquids, and spicy foods is another common strategy. “I stopped drinking hot caffeinated drinks…for several years, and you get out of the habit of drinking them,” says Zuckerman.
LaCroix curates those options at My Meno Plan, which includes a search function where you can enter your symptoms and identify which treatments might work best for you. It also links to published research papers. She says the goal is to empower women with information to make informed decisions about menopause.
A company in England has made a test that picks out the compounds from breath that reveal if people have liver disease.
Every year, around two million people worldwide die of liver disease. While some people inherit the disease, it’s most commonly caused by hepatitis, obesity and alcoholism. These underlying conditions kill liver cells, causing scar tissue to form until eventually the liver cannot function properly. Since 1979, deaths due to liver disease have increased by 400 percent.
The sooner the disease is detected, the more effective treatment can be. But once symptoms appear, the liver is already damaged. Around 50 percent of cases are diagnosed only after the disease has reached the final stages, when treatment is largely ineffective.
To address this problem, Owlstone Medical, a biotech company in England, has developed a breath test that can detect liver disease earlier than conventional approaches. Human breath contains volatile organic compounds (VOCs) that change in the first stages of liver disease. Owlstone’s breath test can reliably collect, store and detect VOCs, while picking out the specific compounds that reveal liver disease.
“There’s a need to screen more broadly for people with early-stage liver disease,” says Owlstone’s CEO Billy Boyle. “Equally important is having a test that's non-invasive, cost effective and can be deployed in a primary care setting.”
The standard tool for detection is a biopsy. It is invasive and expensive, making it impractical to use for people who aren't yet symptomatic. Meanwhile, blood tests are less invasive, but they can be inaccurate and can’t discriminate between different stages of the disease.
In the past, breath tests have not been widely used because of the difficulties of reliably collecting and storing breath. But Owlstone’s technology could help change that.
The team is testing patients in the early stages of advanced liver disease, or cirrhosis, to identify and detect these biomarkers. In an initial study, Owlstone’s breathalyzer was able to pick out patients who had early cirrhosis with 83 percent sensitivity.
Boyle’s work is personally motivated. His wife died of colorectal cancer after she was diagnosed with a progressed form of the disease. “That was a big impetus for me to see if this technology could work in early detection,” he says. “As a company, Owlstone is interested in early detection across a range of diseases because we think that's a way to save lives and a way to save costs.”
How it works
In the past, breath tests have not been widely used because of the difficulties of reliably collecting and storing breath. But Owlstone’s technology could help change that.
Study participants breathe into a mouthpiece attached to a breath sampler developed by Owlstone. It has cartridges are designed and optimized to collect gases. The sampler specifically targets VOCs, extracting them from atmospheric gases in breath, to ensure that even low levels of these compounds are captured.
The sampler can store compounds stably before they are assessed through a method called mass spectrometry, in which compounds are converted into charged atoms, before electromagnetic fields filter and identify even the tiniest amounts of charged atoms according to their weight and charge.
The top four compounds in our breath
In an initial study, Owlstone captured VOCs in breath to see which ones could help them tell the difference between people with and without liver disease. They tested the breath of 46 patients with liver disease - most of them in the earlier stages of cirrhosis - and 42 healthy people. Using this data, they were able to create a diagnostic model. Individually, compounds like 2-Pentanone and limonene performed well as markers for liver disease. Owlstone achieved even better performance by examining the levels of the top four compounds together, distinguishing between liver disease cases and controls with 95 percent accuracy.
“It was a good proof of principle since it looks like there are breath biomarkers that can discriminate between diseases,” Boyle says. “That was a bit of a stepping stone for us to say, taking those identified, let’s try and dose with specific concentrations of probes. It's part of building the evidence and steering the clinical trials to get to liver disease sensitivity.”
Sabine Szunerits, a professor of chemistry in Institute of Electronics at the University of Lille, sees the potential of Owlstone’s technology.
“Breath analysis is showing real promise as a clinical diagnostic tool,” says Szunerits, who has no ties with the company. “Owlstone Medical’s technology is extremely effective in collecting small volatile organic biomarkers in the breath. In combination with pattern recognition it can give an answer on liver disease severity. I see it as a very promising way to give patients novel chances to be cured.”
Improving the breath sampling process
Challenges remain. With more than one thousand VOCs found in the breath, it can be difficult to identify markers for liver disease that are consistent across many patients.
Julian Gardner is a professor of electrical engineering at Warwick University who researches electronic sensing devices. “Everyone’s breath has different levels of VOCs and different ones according to gender, diet, age etc,” Gardner says. “It is indeed very challenging to selectively detect the biomarkers in the breath for liver disease.”
So Owlstone is putting chemicals in the body that they know interact differently with patients with liver disease, and then using the breath sampler to measure these specific VOCs. The chemicals they administer are called Exogenous Volatile Organic Compound) probes, or EVOCs.
Most recently, they used limonene as an EVOC probe, testing 29 patients with early cirrhosis and 29 controls. They gave the limonene to subjects at specific doses to measure how its concentrations change in breath. The aim was to try and see what was happening in their livers.
“They are proposing to use drugs to enhance the signal as they are concerned about the sensitivity and selectivity of their method,” Gardner says. “The approach of EVOC probes is probably necessary as you can then eliminate the person-to-person variation that will be considerable in the soup of VOCs in our breath.”
Through these probes, Owlstone could identify patients with liver disease with 83 percent sensitivity. By targeting what they knew was a disease mechanism, they were able to amplify the signal. The company is starting a larger clinical trial, and the plan is to eventually use a panel of EVOC probes to make sure they can see diverging VOCs more clearly.
“I think the approach of using probes to amplify the VOC signal will ultimately increase the specificity of any VOC breath tests, and improve their practical usability,” says Roger Yazbek, who leads the South Australian Breath Analysis Research (SABAR) laboratory in Flinders University. “Whilst the findings are interesting, it still is only a small cohort of patients in one location.”
The future of breath diagnosis
Owlstone wants to partner with pharmaceutical companies looking to learn if their drugs have an effect on liver disease. They’ve also developed a microchip, a miniaturized version of mass spectrometry instruments, that can be used with the breathalyzer. It is less sensitive but will enable faster detection.
Boyle says the company's mission is for their tests to save 100,000 lives. "There are lots of risks and lots of challenges. I think there's an opportunity to really establish breath as a new diagnostic class.”