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Bidirectional private automated contact tracing

posted Apr 8, 2020, 8:08 PM by Kevin Esvelt   [ updated Apr 8, 2020, 8:09 PM ]

Tracing and isolating the contacts of infected individuals to prevent downstream transmission has proven critical to effective pandemic control. Every country that has succeeded in limiting the spread of SARS-CoV-2 has relied heavily on contact tracing. Nations with little experience have struggled.

Private automated contact tracing (PACT), in which smartphones are used to notify people who may have been exposed by infected individuals while preserving the privacy of both parties, offers considerable advantages in scale and efficiency. It also protects everyone's anonymity better than the traditional form: not even health workers need to know who came in contact with whom. There's just one problem: everyone seems to assume we will use it to perform traditional contact tracing more effectively.

I suspect that we can do much better.

I'm a member of the MIT Safe Paths and PACT groups who have been developing relevant apps and protocols, and helped both of them connect with another group, Covid-Watch/CoEpi. To all of them I've advocated for one key feature: contact logs that are stored for many weeks. The reason is that contact tracing should be bidirectional.

Think of transmission as a family tree: each infected "generation" of people transmit the virus to the next generation of victims. During a pandemic, the family tree rapidly expands, as the average person infects more than one other individual. Some people might have dozens of "offspring"; others may have none. Traditional contact tracing only goes in the "forward" direction: it seeks to find the offspring of known infected individuals and isolate them so they don't spread the virus. But we could also use it in the other direction to find the "parent" of each infected individual.

By finding previously unidentified carriers from earlier generations, "reverse" contact tracing could discover entirely new branches of the transmission tree and isolate individuals known to be contagious by tracing each newly discovered past branchpoint out to the most recent generation.

That is not the case for SARS-CoV-2, for which somewhere between 1 in 6 and 1 in 2 carriers remain completely asymptomatic - yet still contagious. There are no warning signs indicating that these people should get tested, so they don't. These carriers are one major reason we observe so much community transmission with no obvious source of infection.

With bidirectional contact tracing, we have a chance to find asymptomatic carriers. Suppose Bob develops symptoms and tests positive for COVID-19 (or has a fever, which is highly indicative of infection under lockdown conditions when other pathogens are suppressed). With traditional forward contact tracing, we might identify Alice as someone who was exposed by Bob and advise her to self-isolate. With PACT in place, we could afford to trace in the other direction: we could notify Charlie, who was in contact with Bob around the time that he was probably infected, that he should get a serological test to see if he has antibodies to SARS-CoV-2.

If Charlie tests positive, he becomes our new "index case", and we repeat bidirectional contact tracing. "Forward" tracing might notify Beatriz and Brianna, who like Bob were infected by Charlie, as well as the people they infected: Aaron, Adam, Andrew, Alan, Alyssa, and Arianna, all of them "cousins" of Alice. We might even notify David, who infected Charlie, and through him Cameron and Cassie and Chelsea and their "descendants", ultimately limiting the spread of an even larger and previously undiscovered branch of the viral transmission tree.

The implementation of bidirectional contact tracing using a PACT protocol could be a powerful preventive tool in curtailing the spread of SARS-CoV-2. Just as importantly, it could defend against future pandemics that might be considerably more destructive. Indeed, coupled with a monitoring network that screens random people by next-gen sequencing to detect novel zoonoses or engineered agents, bidirectional PACT could become a powerful defense against almost any potential pandemic pathogen.

Our anti-pandemic efforts

posted Apr 3, 2020, 8:01 AM by Kevin Esvelt   [ updated Apr 4, 2020, 7:40 AM ]

For the last several weeks, numerous members of our group, all volunteers, have been working to develop a novel antiviral therapeutic that could also be turned into a gene therapy vaccine. 

The rationale: our group has access to computational and laboratory methods of evolving proteins extremely quickly, so we're attempting to generate "decoy" versions of the receptor used by SARS-CoV-2 that bind the virus even more tightly. This is promising because the virus can't readily escape: it needs to bind that receptor to enter cells. 

To be clear, decoy receptor concept is an old idea, but we think we can do it faster than most, ideally in just weeks. 

 We also have a novel design goal: our sACE2 candidates are being evolved to minimize all interactions with the body's native signaling pathways, meaning we could give patients very high doses to completely block infection without worrying about side effects. If we can succeed quickly and move it to clinical trials, it could save a lot of lives from COVID-19. 

It could also help the future by pointing towards what biodefense programs like BARDA should do next: fund development of mimics for all receptors known to be used by human viruses and potential species-jumping animal viruses. 

The best current description of our plan is our NIH proposal, which we'll be submitting on nearly the last eligible day because we've been so busy getting the work moving. We're deeply grateful to our collaborators in Ed Boyden's group as well as Sebastian Carrasco, the lead veterinary pathologist at MIT's Division of Comparative Medicine, for their amazing contributions to the shared effort. 

We currently don't have dedicated funding for any of our anti-COVID projects and have been burning through our discretionary reserves to make this happen, so if you'd like to support this project, you can do so here. All funds will be used to fight the pandemic; this is our only ongoing laboratory effort.

Kevin and others have also been working on out-of-lab collaborations such as Safe Paths, Saving Face, and Secure DNA, all highly relevant to fighting pandemics. No single technology will solve the problem. But all of humanity is focused on a single problem. Together, we might not just extinguish the biological wildfire that is COVID-19. That's thinking far too small. We should aim to end human pandemics - forever.

Covid-19 pandemic

posted Mar 8, 2020, 9:04 AM by Kevin Esvelt   [ updated Mar 8, 2020, 9:04 AM ]

Message sent to the MIT Media Lab list on preparing for the nascent pandemic on March 4, 2020


This message is intended to provide a general assessment of the global situation and help organize our collective response.

There is a great deal of information floating around on COVID-19, only some of it accurate. Many people claim that it's just a bad flu and the world is overreacting. Others believe it’s more dangerous than the 1918 influenza pandemic that caused the deaths of 50 million people. The truth is almost certainly somewhere in between.

Before I summarize what is known: this is a societal challenge, and the Lab can help.

This is not a foreign issue. It has nothing to do with race or ethnicity or cultural background.

The virus is in over 76 countries, and is now in the Boston area. Let's not panic. Let’s take action.

Agenda item 1: Discuss how we can help keep our community members safe. Item 2: Identify all relevant Lab projects and find ways to leverage them swiftly to help others. Bring your creativity and a list of ongoing efforts or expertise that you think might be useful.

 

What we know

  • The novel coronavirus SARS-CoV-2, which causes COVID-19 disease, is spreading worldwide

  • Everyone appears susceptible: the virus is new to humans, having jumped from an animal

  • The typical victim infects 2-2.5 other individuals depending on patterns of contact

  • Symptoms include fever (87.9%), dry cough (67.7%), fatigue (38.1%), sputum in the lungs (33.4%), shortness of breath (18.6%), sore throat (13.9%), headache (13.6%), bone pain (14.8%), chills (11.4%), nausea or vomiting (5.0%), nasal congestion (4.8%), diarrhea (3.7%)

  • 8 of 10 victims experience mild symptoms; 13.8% moderate to severe; 6% need hospital care

  • People without symptoms shed virus and can infect others

  • Risk level increases very sharply with age and ill health; children are almost never affected

  • ~6.7% of victims ages 15-49 need hospital care, but only 2% of those need an ICU

  • Some regions have shown that good hospital care can keep the overall death rate below 2%

  • The local mortality rate can rise to 5.8% if the healthcare system is overwhelmed

  • Imposing cordons sanitaires and isolation measures can halt transmission for the duration

  • A vaccine will not be widely available for 12-18 months; antivirals may arrive earlier

  • Those recovered are likely to be resistant for at least a year, but probably not more than 3 years

Therefore, our goal as a society is to keep too many people from getting infected at once. We need to ensure that there will be enough hospital beds for everyone who falls ill if the pandemic continues to spread, which appears likely but not certain. 

That starts here at the Lab.

Community health

We can protect our friends and colleagues by minimizing local transmission. For example:

  • Never shake hands! An elbow bump or a polite bow will suffice

  • Frequently wash your hands for 20 seconds with soap and water

  • Use hand sanitizer often, including to clean your phone

  • Clean commonly used objects with wipes and keep doors propped open as much as possible

  • Get a flu shot now if you haven't had one, as flu patients often also need hospital beds

  • If you feel sick in any way for any reason, stay home!

  • If you need healthcare, ask to be tested for infection, and alert MIT Medical if it's positive

To anyone who can’t find hand sanitizer in stores, you can make it yourself:

Hand sanitizer recipe:

  • 2/3 cup 99% isopropanol

  • 1/3 cup aloe vera gel

  • Mix thoroughly and pour into a small bottle to carry

What about cleaning agents?

  • Alcohol inactivates >99.9% of coronaviruses in <1 sec

  • Bleach is less effective, requiring longer to take effect, but most other disinfectants work well

  • Using wipes and cleaners is important, as coronaviruses can linger on surfaces for 2-9 days 

Risk assessment

Statistically, we’re unlikely to have been exposed as yet, but we should take precautions immediately.

There are almost certainly unidentified carriers in the Boston metro area, and the number is likely to grow rapidly, as occurred in Seattle. Keep in mind that the U.S. has not been testing widely, meaning that we should not expect to detect community transmission until there are hospital cases with no obvious source.

If we conservatively assume each victim infects two others 7 days after being infected, and there are 20 carriers in the Boston area this week, then there will be 20,000 newly infected individuals in ten weeks. That assumes transmission does not abate in the interim, which may occur; coronavirus is somewhat seasonal, but much less so than flu. We should hope for the best, but prepare for the worst.

One can hope that local officials will take action before we reach 20,000 active new cases in the area. Those preventive actions will keep us safer, but are also likely to impact our research. We should plan for that.

Preparations

It’s fairly likely that public transit will be closed, and large gatherings discouraged. A (non-peer reviewed) assessment determined that those were probably the most effective of the measures imposed in China.

MIT may advise nonessential personnel to avoid campus this summer, or even sooner. University campuses in China have been closed for some time, with classes conducted remotely. Just in case, it may be prudent to focus on those aspects of your research that require your physical presence, and start thinking about how you could work remotely. Again, hope for the best, but prepare for the worst.

It's possible that schools will close. They are now closed in China, South Korea, Japan, and Italy, but have reopened in Taiwan. Whether Taiwan’s rate of transmission differs may determine whether they are also closed here. Since high schoolers are known to be vulnerable, it’s more likely that high schools will be closed than elementary schools, but we don’t know as yet. This may impact the parents among us. It’s also one of the areas where the Lab’s expertise could make a considerable difference.

Finally, anyone who is infected will need to self-isolate in their home for at least 14 days. Water shouldn’t be a problem, and food deliveries are likely to continue, but it’s not a bad idea to buy a little extra when grocery shopping to prepare, and it's worth ensuring that you have a reasonable supply of any essential medications. As always, hope for the best, but prepare for the worst, at least within reason.

 

Summary

These events may have a major impact on society and our daily lives. Our actions and especially our research can help mitigate those impacts, if not here then elsewhere in the world. We have an opportunity to make a difference. 

 

Disclaimer

I am not a medical doctor or epidemiologist, but a generalist whose research overlaps with a number of relevant fields, including pandemic disease. I do not speak for the Lab’s Executive Committee or for MIT leadership. All assessments and opinions are my own or linked from a more knowledgeable source.

Let me know if you have any questions or concerns. 

 

---

Kevin M. Esvelt, Ph.D.

Leader, Sculpting Evolution Group

Assistant Professor, MIT Media Lab

Massachusetts Institute of Technology


Moral responsibilities for animal suffering

posted May 28, 2018, 6:43 PM by Kevin Esvelt   [ updated May 28, 2018, 6:52 PM ]

There is a clear moral case for Africans to make use of gene drive to help eradicate malaria, but what of the non-humans who suffer? In Leaps Magazine, I ask difficult questions concerning the power of new technologies and our responsibility for the consequences of choosing not to use them - in this case, for animal suffering.

In tribute

posted Jan 9, 2018, 7:15 AM by Kevin Esvelt   [ updated Jan 9, 2018, 7:15 AM ]

The currents of time carry us onwards, until the day comes when we can swim no longer. We are not wholly gone, for the ripples of our actions continue to touch the lives of others, a pattern whose breadth and beauty defines us.

Few patterns are as beautiful as that of Ben Barres.

I met Ben in person only once, in 2014. After that singular meeting we continued to correspond, often enough that I considered him a mentor. Even so, I cannot say I knew him well.

One need not know a person well to see their inner light.

Much has been written of Ben's passion, courage, and brilliance. There are several lovely epitaphs to his life and work – ethical, social, and scientific – woven from tales shared by those whose lives he touched.

One of his last efforts was a public call to ensure that postdocs can take their projects with them when they start their own labs, free of competition from their former advisor. In Ben's memory, this is a pledge I make gladly.

We will not see his like again.

Aotearoa: Mistakes and Amends

posted Jan 9, 2018, 7:13 AM by Kevin Esvelt   [ updated Jan 9, 2018, 7:13 AM ]

Publicly acknowledging a failure and trying to make amends can strengthen moral resolve. On November 16, I failed my partners.

Researchers should hold themselves morally accountable for all of the consequences of their work. That can require publicly acknowledging when we have done wrong and striving to make amends.

In trying to remedy a past error - my suggestion that self-propagating CRISPR gene drive might be used for invasive species control - I singularly failed to uphold the ideals of Responsive Science.

It was inexcusably wrong of me to publish a manuscript relating to gene drive and Aotearoa New Zealand without thinking to invite my new Māori partners to offer suggestions during the revision stage. My mistake could jeopardize a primary goal of our partnership: to ensure that daisy drive can only be developed and considered for use in Aotearoa under a co-governance model with Māori, the kaitiaki (caretakers) of the sacred taonga species.

As Melanie Mark-Shadbolt said of me (quoting with permission):

"... his naivety of the political situation Māori are in, and the publication of this paper without talking to the other partner (Māori) more than likely will have consequences for that partner (Māori) that the author (Esvelt) did not consider."

Her words are searingly true. This is precisely why Māori co-governance of daisy drive development is necessary if the method is ever to be used in Aotearoa: I know as little of the local ecosystem as I do of the local politics, meaning that I cannot possibly evaluate the likely consequences. It is why the matauranga Māori, the wisdom and way of knowing of the Māori people accumulated over generations in Aotearoa, will be essential to help ensure that any action taken is in the best interests of the taonga species.

She goes on:

"Pessimistically, it is now possible that Māori may never get co-governance in the discussion and/or development of gene-drive technologies in Aotearoa. Optimistically, however, this paper could be a wake-up call that the science sector in Aotearoa New Zealand needs to work in partnership with Māori and preserve New Zealand’s leadership on the world stage."

I hope that the latter will be true, but hope is not enough. Since I did not think to invite suggestions on a matter relevant to our partnership, I must hold myself responsible for any consequences of my thoughtlessness. That requires publicly acknowledging my failure, attempting to make amends, and striving to better uphold my duties in future.

Acknowledging mistakes is painful, but honesty requires it: better that we publicly admit wrongdoing and strengthen our resolve than continue to do wrong.

In February 2018, I will be meeting with Te Tira Whakamātaki (the Māori biosecurity network) and the Te Herenga Māori (the Māori National Network). At those meetings, I will bring up this story of my failure because it illustrates the necessity of inviting local wisdom and governance. It is my hope that hearing diverse Māori and New Zealander perspectives will not only aid my understanding of whether and how my inventions may benefit Aotearoa, but also shed light on how I might best fulfill my broader responsibilities to the world beyond.

The morality of nature

posted Jan 20, 2017, 3:15 PM by Kevin Esvelt   [ updated Jan 9, 2018, 7:12 AM ]

I've received many communications in response to the profile by Michael Specter in the New Yorker; more than I can answer. They've all been quite positive except for one topic: my comments on the morality of the natural world. One reader wrote:

'One topic that has been really bothering me though is your views on morality and nature. One should not anthropomorphize nature or natural selection and look at it in terms of good or bad, nature just IS, nature is balanced, that's it. As soon as humans intervene is when it becomes unbalanced, its up to you to decide how unbalanced we are willing to make it.

I guess my point is gene editing can be an incredible tool for good to humans but someone with your intelligence and power shouldn't be saying things like “the ridiculous notion that natural and good are the same thing.” or “Natural selection is heinously immoral.” Saying nature is immoral is just as wrong as equating nature to godliness.'

This is an issue deserving of in-depth exploration, so I'm sharing a slightly edited version of my reply:

I agree that nature is value neutral. I normally use the term amoral, not immoral, but only as long as we lack the power to influence it. Once we do, it becomes a test of our own moral character.

If failing to save a drowning child when we could have done so makes us responsible for that child's death, then acquiring the ability to mitigate animal suffering renders us morally responsible if we choose not to.

This is not a comfortable moral position. Right now, we spend ~$2.5 billion per year in the US on animal shelters and trap-neuter-release programs for stray and feral dogs and cats. Three weeks ago I rescued a limping stray cat. Had she not received care and antibiotics, she would likely have lost the ability to hunt and slowly starved due to her badly infected wound. How is that stray cat different from an ocelot cub stricken with a screwworm infection, which is unimaginably more painful? We didn't deliberately create either, but we can do something about the stray cat, but cannot aid the ocelot. Of course, that will not be true for much longer: we eradicated the screwworm from North America with sterile insect technique, and with gene drive could do the same for South America. Should we?

We must face this question openly. It doesn't obviate the other challenges, such as weighing humans against animals or how much more of a say South Americans should have in the case of screwworm. But since we are now developing the power to intervene, it becomes a moral issue where previously it was not.

That's why we need to discuss these challenges now, and why all research on these questions should be done in the open. It's not my decision to make, or yours, but everyone's. I need you as a check on my own intuitions, because I am not confident in my own ability to make wise decisions on this scale. We must face it together.

Why Open Science?

posted Dec 8, 2016, 11:39 AM by Kevin Esvelt   [ updated Dec 26, 2016, 8:12 AM ]

Most researchers keep their plans to themselves for a very good reason: the system punishes us if we don't. Share a brilliant idea, and another laboratory can throw more money and hands at the problem, publish first, and claim all of the credit.

Secretive research is not just wasteful and inefficient from the perspective of society. It's actively miserable for practicing scientists. Because no one shares the results of failed experiments, different labs fall into the same pit traps over and over again. We never hear about new successes or techniques until the project is complete, so it can take years to find out that the potential collaborator with a key piece of the puzzle was always just down the street. Since we only have the vaguest idea what others are working on, we always worry that someone else might be working on the same project. If they get there first, we've been 'scooped' and typically get nothing. Even if we publish first, we've still wasted years on a project that someone else would have completed soon afterwards. Paranoid secrecy may be fun in a game; less so when your life's work is at stake.

The harsh truth is that no one would rationally design the current scientific enterprise. It evolved in the time before modern communication technologies, and persists due to cultural traditions and a collective action problem. It's as though we're still sending out competing teams of explorers who still insist on returning with maps and reports every few years... even though all of them now have satellite uplinks.

That would be bad enough, but there's more. Our civilization, being unsustainable, quite literally depends on new technological advances. Those advances are getting more powerful with time. But who decides whether an advance will be positive or negative? The small team of ultra-specialist explorers, who can't reliably anticipate the consequences on their own.

There's evidence that risk analyses involving local citizens produce more comprehensive results than teams of expert risk analysts, even as judged by those same experts. But in an age of increasing dependence on successively more powerful technologies, we still practice science much as we did a century ago – that is, mostly blind to the ongoing efforts of others and any attempts to assess consequences. It's mind-bogglingly shortsighted, and a testament to the power of the status quo bias and collective action problems.

Of course, this doesn't mean we should reform all of science immediately, even if we could. We have a limited ability to predict the consequences of altering complex systems, including the scientific enterprise. That means we should start small, carefully measure outcomes, and only scale up if warranted.

The field of gene drive research is an ideal test case. Conducting gene drive experiments behind closed doors risks affecting the shared environment and the lives of others without their knowledge or consent. It denies other scientists and interested citizens the opportunity to voice suggestions or concerns that could improve safety and accelerate progress. And it greatly reduces our ability to build support for beneficial applications. In short, there are compelling moral and practical reasons for ensuring that gene drives and other ecological technologies are developed in the open light of day.

Opening science from the earliest stages will enhance safety and reliability by encouraging collective scrutiny of safeguards and research plans. It will accelerate scientific progress by enabling coordination among researchers. And it can improve public confidence and the likelihood of balanced assessment by actively inviting and addressing concerns early in development. For the field of gene drive research, open and responsive science is a moral and practical necessity.

That's why we're sharing all of our research proposals that involve gene drive here. Special thanks to all the other members of Sculpting Evolution for their courage - they're the ones placing their careers on the line in order to do what is right.

We hope that this step will help encourage journals, funders, holders of intellectual property, and policymakers to change scientific incentives in favor of open gene drive research.

Boldly Illuminating a Better Future

posted Nov 16, 2016, 6:35 PM by Kevin Esvelt   [ updated Dec 30, 2016, 1:31 PM ]

We've submitted an application to the Roddenberry Prize competition on behalf of the Responsive Science Project.  Our platform isn't live just yet, but our goal - an open and community-responsive scientific enterprise - is perfectly in alignment with the shared vision set out by Gene Roddenberry and his successors.

More details on our reasoning, as well as copies of our grant proposals involving gene drive, are available on our proposals page.

Belated update

posted Oct 25, 2016, 9:42 AM by Kevin Esvelt   [ updated Nov 18, 2016, 12:20 PM ]

As is hopefully evident from the site changes and main news page, we've now launched the Sculpting Evolution Group at the MIT Media Lab. We're at the Lab because it's one of the very few places where we can our work in a thoughtful and ethical manner. That is, a place that will actively support us in evaluating the consequences of our technologies and pioneering new ways to make science better serve society rather than strictly focusing on scientific publications.

In the tumult of setting up the lab and attempting to guide gene drive technology and new developments, posting has suffered more than a bit. Recent thoughts have been published at Project Syndicate and Nature, although most of my output has been in the form of talks - 38 of them so far this year. I'm hoping to make most of the presentations available. As always, everything is CC-BY.

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