Can Synthetic Biology Save Us? This Scientist Thinks So.
Drew Endy is squarely focused on the potential of redesigning organisms for useful purposes. He also acknowledges significant challenges.
When the family house in Devon, Pa., caught fire, Drew Endy, then 12, carried out his most cherished possession — his personal computer.
Years later, as a graduate student, Mr. Endy was accepted to Ph.D. programs in biotechnology and political science.
The episodes seem to sum up Mr. Endy, a most unusual scientist: part engineer, part philosopher, whose conversation is laced with references to Descartes and Dylan, as well as DNA.
He’s also an evangelist of sorts. Mr. Endy, a 51-year-old professor of bioengineering at Stanford University, is a star in the emerging field of synthetic biology. He is its most articulate enthusiast, inspiring others to see it as a path to a better world, a transformational technology to feed the planet, conquer disease and combat pollution.
The optimism behind synthetic biology assumes that biology can now largely follow the trajectory of computing, where progress was made possible by the continuous improvement in microchips, with performance doubling and price dropping in half every year or two for decades. The underlying technologies for synthetic biology — gene sequencing and DNA synthesis — are on similar trends.
As in computing, biological information is coded in DNA, so it can be programmed — with the goal of redesigning organisms for useful purposes. The aim is to make such programming and production faster, cheaper and more reliable, more an engineering discipline with reusable parts and automation and less an artisanal craft, as biology has been.
Synthetic biology, proponents say, holds the promise of reprogramming biology to be more powerful and then mass-producing the turbocharged cells to increase food production, fight disease, generate energy, purify water and devour carbon dioxide from the atmosphere.
“Biology and engineering are coming together in profound ways,” Mr. Endy said. “The potential is for civilization-scale flourishing, a world of abundance not scarcity, supporting a growing global population without destroying the planet.”
That idyllic future is decades off, if it is possible at all. But in the search for the proverbial next big thing over the next 20 years, synthetic biology is a prime candidate. And no one makes the case more persuasively than Mr. Endy.
What You’re Doing Right Now Is Proof of Quantum Theory
Running a computer underscores how quantum physics is remaking our world.
Nobody understands quantum mechanics,” Richard Feynman famously said. Long after Max Planck’s discovery in 1900 that energy comes in separate packets or quanta, quantum physics remains enigmatic. It is vastly different from how things work at bigger scales, where objects from baseballs to automobiles follow Newton’s laws of mechanics and gravitation, consistent with our own bodily experiences. But at the quantum level, an electron is a particle and a wave, and light is a wave and a particle (wave-particle duality); an electron in an atom takes on only certain energies (energy quantization); electrons or photons can instantaneously affect each other over arbitrary distances (entanglement and teleportation); a quantum object exists in different states until it is measured (superposition, or popularly, Schrödinger’s cat); and a real physical force emerges from the apparent nothingness of vacuum (the Casimir effect).
For a theory that nobody understands, quantum physics has changed human society in remarkable ways.1 It lies behind the digital technology of integrated circuit chips, and the new technology of light-emitting diodes moving us toward a greener world. Scientists are now excited by one of the more elusive notions in quantum physics, the idea of ephemeral “virtual” photons, which could make possible non-invasive medical methods to diagnose the heart and brain. These connections illustrate the flow of ideas from scientific abstraction to useful application. But there is also a counter flow, where pragmatic requirements generate deep insight. The universal laws of thermodynamics have roots in efforts by 19th-century French engineer Sadi Carnot to make the leading technology of the time, the steam engine, more efficient. Similarly, the growth of quantum technology leads to deeper knowledge of the quantum. The interplay between pure theory, and its outcomes in the everyday world, is a continuing feature of science as it develops. In quantum physics, this interaction traces back to one of its founders, Danish physicist Niels Bohr.
A Cure for Type 1 Diabetes? For One Man, It Seems to Have Worked.
A new treatment using stem cells that produce insulin has surprised experts and given them hope for the 1.5 million Americans living with the disease.
Brian Shelton may be the first person cured of Type 1 diabetes. “It’s a whole new life,” Mr. Shelton said. “It’s like a miracle.”Credit...
Brian Shelton’s life was ruled by Type 1 diabetes.
When his blood sugar plummeted, he would lose consciousness without warning. He crashed his motorcycle into a wall. He passed out in a customer’s yard while delivering mail. Following that episode, his supervisor told him to retire, after a quarter century in the Postal Service. He was 57.
His ex-wife, Cindy Shelton, took him into her home in Elyria, Ohio. “I was afraid to leave him alone all day,” she said.
Early this year, she spotted a call for people with Type 1 diabetes to participate in a clinical trial by Vertex Pharmaceuticals. The company was testing a treatment developed over decades by a scientist who vowed to find a cure after his baby son and then his teenage daughter got the devastating disease.
Mr. Shelton was the first patient. On June 29, he got an infusion of cells, grown from stem cells but just like the insulin-producing pancreas cells his body lacked.
Now his body automatically controls its insulin and blood sugar levels.
Mr. Shelton, now 64, may be the first person cured of the disease with a new treatment that has experts daring to hope that help may be coming for many of the 1.5 million Americans suffering from Type 1 diabetes.
“It’s a whole new life,” Mr. Shelton said. “It’s like a miracle.”
Diabetes experts were astonished but urged caution. The study is continuing and will take five years, involving 17 people with severe cases of Type 1 diabetes. It is not intended as a treatment for the more common Type 2 diabetes.
“We’ve been looking for something like this to happen literally for decades,” said Dr. Irl Hirsch, a diabetes expert at the University of Washington who was not involved in the research. He wants to see the result, not yet published in a peer-reviewed journal, replicated in many more people. He also wants to know if there will be unanticipated adverse effects and if the cells will last for a lifetime or if the treatment would have to be repeated.
But, he said, “bottom line, it is an amazing result.”
Researchers can now design and mass-produce genetic material — a technique that helped build the mRNA vaccines. What could it give us next?
Ten years ago, when Emily Leproust was a director of research at the life-sciences giant Agilent, a pair of scientist-engineers in their 50s — Bill Banyai and Bill Peck — came to her with an idea for a company. The Bills, as they were later dubbed, were biotech veterans. Peck was a mechanical engineer by training with a specialty in fluid mechanics; Banyai was a semiconductor expert who had worked in genomics since the mid-2000s, facilitating the transition from old-school Sanger sequencing, which processes a single DNA fragment at a time, to next-generation sequencing, which works through millions of fragments simultaneously. When the chemistry was miniaturized and put on a silicon chip, reading DNA became fast, cheap and widespread. The Bills, who met when Banyai hired Peck to work on a genomics project, realized that there was an opportunity to do something analogous for writing DNA — to make the process of making synthetic genes more scalable and cost-effective.
At the time, DNA synthesis was a slow and difficult process. The reagents — those famous bases (A’s, T’s, C’s and G’s) that make up DNA — were pipetted onto a plastic plate with 96 pits, or wells, each of which held roughly 50 microliters, equivalent to one eyedropper drop of liquid. “In a 96-well plate, conceptually what you have to do is you put liquid in, you mix, you wait, maybe you apply some heat and then take the liquid out,” Leproust says. The Bills proposed to put this same process on a silicon chip that, with the same footprint as a 96-well plate, would be able to hold a million tiny wells, each with a volume of 10 picoliters, or less than one-millionth the size of a 50-microliter well.
Because the wells were so small, they couldn’t simply pipette liquids into them. Instead, they used what was essentially an inkjet printer to fill them, distributing A’s, T’s, C’s and G’s rather than pigmented inks. A catalyst called tetrazole was added to bind bases into a single-strand sequence of DNA; advanced optics made perfect alignment possible. The upshot was that instead of producing 96 pieces of DNA at the same time, they could now print millions.
The concept was simple, but, Leproust says, “the engineering was hard.” When you synthesize DNA, she explains, the yield, or success rate, goes down with every base added. A’s and T’s bond together more weakly than G’s and C’s, so DNA sequences with large numbers of consecutive A’s and T’s are often unstable. In general, the longer your strand of DNA, the greater the likelihood of errors. Twist Bioscience, the company that Leproust and the Bills founded, currently synthesizes the longest DNA snippets in the industry, up to 300 base pairs. Called oligos, they can then be joined together to form genes.
Today Twist charges nine cents a base pair for DNA, a nearly tenfold decrease from the industry standard a decade ago. As a customer, you can visit the Twist website, upload a spreadsheet with the DNA sequence that you want, select a quantity and pay for it with a credit card. After a few days, the DNA is delivered to your laboratory door. At that point, you can insert the synthetic DNA into cells and get them to begin making — hopefully — the target molecules that the DNA is coded to produce. These molecules eventually become the basis for new drugs, food flavorings, fake meat, next-gen fertilizers, industrial products for the petroleum industry. Twist is one of a number of companies selling synthetic genes, betting on a future filled with bioengineered products with DNA as their building blocks.
In a way, that future has arrived. Gene synthesis is behind two of the biggest “products” of the past year: the mRNA vaccines from Pfizer and Moderna. Almost as soon as the Chinese C.D.C. first released the genomic sequence of SARS-CoV-2 to public databases in January 2020, the two pharmaceutical companies were able to synthesize the DNA that corresponds to a particular antigen on the virus, called the spike protein. This meant that their vaccines — unlike traditional analogues, which teach the immune system to recognize a virus by introducing a weakened version of it — could deliver genetic instructions prompting the body to create just the spike protein, so it will be recognized and attacked during an actual viral infection.
As recently as 10 years ago, this would have been barely feasible. It would have been challenging for researchers to synthesize a DNA sequence long enough to encode the full spike protein. But technical advances in the last few years allowed the vaccine developers to synthesize much longer pieces of DNA and RNA at much lower cost, more rapidly. We had vaccine prototypes within weeks and shots in arms within the year.
Now companies and scientists look toward a post-Covid future when gene synthesis will be deployed to tackle a variety of other problems. If the first phase of the genomics revolution focused on reading genes through gene sequencing, the second phase is about writing genes. Crispr, the gene-editing technology whose inventors won a Nobel Prize last year, has received far more attention, but the rise of gene synthesis promises to be an equally powerful development. Crispr is like editing an article, allowing us to make precise changes to the text at specific spots; gene synthesis is like writing the article from scratch.
Biden’s Democracy Conference Is About Much More Than Democracy
While Americans angry about the results of the 2020 election were busy storming their own Capitol and conducting the umpteenth recount in Arizona, threats from outside the country didn’t take a lunch break. To the contrary, they are evolving rapidly.
Imagine a hostile country shutting down New York City’s electrical grid for months at a time using code-breaking quantum computers. Imagine pirates in cyberspace disabling American missile defense systems without warning. Imagine China obtaining the private health data or private phone communications of millions of Americans, including members of Congress.
These aren’t nutty hypotheticals in some distant dystopian future. They are scenarios that keep American national security officials up at night right now.
“We have already reached the point where the behaviors of a limited group of talented actors in cyberspace could completely obliterate systems that we rely on for our day-to-day survival,” Candace Rondeaux, a specialist on the future of warfare at New America, a Washington-based think tank, told me.
The Biden administration’s response has been to counter those threats by gathering a coalition of democracies that will work together to safeguard our economies, our militaries and our technological networks from bad actors in China, Russia and elsewhere. That’s the reason President Biden and European counterparts formed the U.S.-E.U. Trade and Technology Council, which established working groups to develop new technology and prevent it from falling into the wrong hands.
It’s the reason Mr. Biden met with the heads of state of Australia, India and Japan — world powers on China’s doorstep — to ensure that “the way in which technology is designed, developed, governed and used is shaped by our shared values and respect for universal human rights.” And it’s the reason Mr. Biden has called together more than 100 leaders from democratic countries around the world for a virtual Summit for Democracy this Thursday and Friday.
At this week’s summit, there will be plenty of familiar-sounding pledges to root out corruption and defend human rights. There is likely to be hand-wringing about coups that reversed fragile progress in Sudan and Myanmar, and condemnations of leaders who used the pandemic as an excuse to crack down on opposition and dissent, including those in El Salvador, Hungary and Uganda.
But at its core, this conference is not just about protecting democracy at home and abroad. It’s also about how open societies will defend themselves in the future against existential technological threats. As countries like China and Russia invest heavily in artificial intelligence and quantum computing, and exercise intensive state control over data, the United States and its allies need a game plan. What rules should be adopted to govern the use of artificial intelligence, quantum computing and space travel? How do we make sure those technologies aren’t weaponized against us?
The Biden administration is attempting to forge a common front with allies in Europe and Asia across technological, economic and military spheres to prepare for an age of technological competition that will look far different from any geopolitical rivalry that the world has ever seen. Democracy is the common thread stringing the Biden administration’s efforts together. It’s the code word for who’s on our team.
The imminent arrival of the long-awaited fourth “Matrix” movie will surely spur another round of thinking about a question that philosophers have been kicking around at least since Plato’s time: How do we know that our world is real? Nowadays, of course, we’re far more likely to consider that a simulated reality would be rendered in bytes rather than shadows on a cave wall. Furthermore, given both the technical progress being made and the business push behind it, far more likely than our predecessors to actually embrace the prospect of life in a virtual world. The philosophical implications of such worlds — as well as the possibility we might already be existing within one — are the subject of the philosopher David J. Chalmers’s new book “Reality+,” which will be published in January. In it, Chalmers, who is a professor of philosophy and neural science at New York University, as well as co-director of the school’s Center for Mind, Brain and Consciousness, argues, among other things, that our thinking about our future virtual lives needn’t be rooted in visions of dystopia. “The possibilities for virtual reality,” says Chalmers, who is 55, “are as broad as the possibilities for physical reality. We know physical reality can be amazing and it can be terrible, and I fully expect the same range for virtual reality.”
The teenager who made medical history to save her mother
When she was just 19, Aliana Deveza organised and underwent an historic operation to save her mum's life.
She persuaded a hospital to do the first organ swap in the United States where different organs were exchanged between unrelated pairs of donors.
"The first thing that I asked when I woke up was just how was my Mom? Is she okay? Did she make it?
"I wasn't really worried about myself anymore, I was just kind of focused on getting through the pain that I was feeling. Just hearing that everybody had made it, I was able breathe again."
When Aliana says everyone else, she's not just talking about herself and her mother, because two other women - sisters - were also having operations.
One of Aliana's organs would go to one of the sister, and one of the sister's kidneys would go to Aliana's mum. Two lives were being, with two people donating organs to strangers to save a family member.
The operation was the result of two years of hard work which paid off. Aliana had saved her mother Erosalyn from years of kidney dialysis, illness and possibly an early death -and a complete stranger would go on to live a new life.
Kidneys are one of the only organs a living person can donate to another, as most of us are born with two but we only need one to function.
Yet people who need a kidney are not always able to take one from someone they love, even if that person is willing to give it.
Across the world around 150,000 organs were transplanted in 2019 - a small fraction of those who need a new organ.
Alvin Roth shared the prize for Economics from the Nobel Foundation in 2012 for his work devising a system to help more people give and get kidneys.
"Unlike many organs its possible for someone to give a kidney to someone they love and save their life," he explains.
"But sometimes they can't take your kidney even though you're healthy enough to give one. And perhaps I'm the donor in a in a similar pair, I would love to give a kidney to someone I love but I can't.
"But maybe my kidney would work for your patient and your kidney would work for my patient. That's the simplest kind of kidney exchange where two donor pairs get together, and each one gets a compatible kidney from the other patients."
The work of Alvin Roth and his colleagues resulted in a system which has been able to scale up the number of kidney swaps, so now each year thousands of lives are saved.
But these organ exchanges are not yet legal everywhere. In Germany, for example, you can still only give an organ directly to someone in your immediate family. One concern is that vulnerable people will be tempted to sell an organ for money.
It's not pairs of people. In some cases chains of people have come together to maximise the number of matched kidneys.
In one case, 70 different people were brought together so 35 donors gave their kidneys to 35 strangers so that others could get a new lease of life.
Aliana wasn't able to swap her kidney with her mother because doctors feared the kidney problems her mum had might be hereditary, so Aliana might have it too.
She still wanted to help her mum get a new kidney but time was running out, so she started to do some research and found it might be possible to swap part of a liver for a kidney.
"I started researching, the type of organs that can be donated while a person was still alive. And the liver is what came up most."
Aliana did not know that this was just a theoretical possibility and was not a regular operation. She started calling hospitals to see if she could donate part of her liver to someone in exchange for a kidney for her mum.
Aliana says a few hospitals did not understand what she meant: "I had a few hospitals transfer me to the morgue, because they didn't know what I was talking about."
Eventually she did get the right person for the job. John Roberts a surgeon at the University of California in San Francisco.
"He didn't just brush it off. I mean, I was just this 19-year-old girl, and I didn't know if I sounded crazy. My family was against it because they didn't want me putting myself in any danger."
With the help of the hospital they found two sisters who would pair with Aliana and her mum. One of the sisters would get part of Aliana's liver, and Aliana's mum would get a new kidney from the other sister.
Aliana has no regrets, so why does she think more of us are not doing it? "I think people gravitate away from the idea of organ donation, because of the fear surrounding it.
"These are major operations, there are definitely a lot of risks, but understanding it and going through the process with a team that will be there for you during the process is what helps."
Small device that might render stethoscope obsolete
The medic sees internal body organs clearly, no longer having to make sense from a cacophony of body sounds
- Advancements in technology have compressed the point-of-care ultrasound to such a degree that handheld, pocket-sized versions are now readily available in Kenya.
- Wachira says the Pocus has not replaced the stethoscope, but has become a standard tool that almost every doctor at Aga Khan carries.
Dr Benjamin Wachira, an emergency care physician at the Aga Khan University Hospital, scans a client's heart at the emergency wing using the point of care ultrasound. The device is now a standard at the hospital, which nearly every doctor carries.
Image: WILFRED NYANGARESI
For many doctors, the good old stethoscope is a symbol of the skill and knowledge they possess.
Yet now, a new diagnostic tool may render the stethoscope obsolete, even in Kenya.
Enter Dr Benjamin Wachira, an emergency care physician at the Aga Khan University Hospital in Nairobi.
Instead of a stethoscope around his neck, he carries a small handheld device that might, in time, relegate the former into the dustbins of medical history.
The gadget is the point-of-care ultrasound (Pocus) device.
“It has been used by radiologists and obstetricians for a long time,” he explains. But advancements have compressed the technology to such a degree that handheld, pocket-sized versions are now readily available in Kenya.
“Before, I would have used the stethoscope to listen to the patient's body and determine if the sounds are normal or there is a problem,” DrDr Wachira explains.
That means he would need to make sense from a cacophony of thumps, crackles, and wheezes from a patient’s body to decide the next course of action.
But at Aga Khan, doctors are now relying more on the Pocus.
It is basically a small probe attached to an Ipad or a mobile phone.
He applies bluish gel on the probe (size of a TV remote) and moves it around the patient’s chest. An image of a healthy heart pumping shows up on the tablet's screen. “Normal,” he says. He moves to the upper right portion of the abdomen. The liver comes up. “Normal,” he says.
“It takes away the guesswork. Before you had to use the stethoscope, listen to the sounds and decide whether to send the patient to the cardiology for a scan or what to do. Sometimes the results would come a week later. But this one helps us make decisions immediately,” he explains.
Wachira says the Pocus has not replaced the stethoscope, but has become a standard tool that almost every doctor at Aga Khan carries.
In fact, for low resource environments, the World Health Organization now recommends portable ultrasound devices as a primary diagnostic tool.
The device uses sound waves to produce pictures of the inside of the body. It is safe, non-invasive, and does not use radiation.
“Every emergency department in any facility should have this,” Dr Wachira says.
He says it is particularly useful in saving accident victims.
“You can easily pick out internal bleeding in the body within two minutes, or injuries to any vital organ. It basically takes away any guesswork,” he explains.
One study in the United States showed that ultrasound correctly identified particular issues in 82 per cent of patients as opposed to a 47 per cent detection rate with physical examination only.
Two weeks ago, Health CAS Mercy Mwangangi encouraged facilities to invest in ultrasound, giving the example of the Aga Khan University Hospital.
She was addressing biomedical engineers at the annual gathering, held in Kakamega.
“There is a gap which can be addressed by you, medical engineers, who know the advances in technology. You can challenge us within the policy table to avail such technologies because I am sure there is a whole field that you are aware of technologies that is happening outside there,” she said.
A random check in Nairobi shows the device will cost around Sh500,000.
You cannot post new topics in this forum You cannot reply to topics in this forum You cannot edit your posts in this forum You cannot delete your posts in this forum You cannot vote in polls in this forum