The Engineering of Biology at MIT

One of the big reunion activities at MIT is Technology Day, a series of lectures from faculty done shortly after commencement.   This year the theme was Synthetic Life, and the talks were just as creepy and interesting as you might expect.

Technology Day panelists, June 10, 2017, Angela Belcher on right

Seven professors spoke on work ranging from designing viruses, to doing self-assembly of nano-structures, to using massive gene editing to find drugs to kill the malaria parasite.

Three new techniques have now made it possible to design lifeforms:

  • Cheap sequencing – the ability to quickly understand what’s in a biological mixture.
  • CRISPR/Cas9 gene editing – a protein borrowed from the cheese-making bacterium Streptococcus thermophilus that lets one replace particular DNA sequences with others.
  • Fast machine pattern recognition – a neural net technique that can find patterns in vast piles of random data.   Recently made feasible by GPU hardware, large datasets, and efficient training algorithms.

CRISPR lets one make a change, the sequencing tells if it takes, and the pattern recognition says if it does something.

Let me summarize the first talks and then concentrate on the last, which was the wackiest:

  • Prof. Linda Griffith wondered why the drug Jun Kinase worked on endometriosis so well in mice, but failed its human trial.  She came up with a way to grow “organoids”, bits of your own tissue grown in a dish, and found that the drug worked great on the 25% of the population with a particular genetic sequence, and failed on the others.  We can now do human trials on bits of our own flesh.
  • Prof. Ron Weiss has found a way to build Boolean logic gates with DNA – structures that when two proteins come in, can express another protein.   Yes, it’s Turing-complete because it can make a NOR gate.  He wants to set up Boolean equations that will let a virus detect the proteins unique to a cancer cell and then turn on and kill it.
  • Prof. Feng Zhang described retro-viral therapy using CRISPR: inject viruses that will edit in naturally occurring sequences that protect against HIV and cardiovascular problems.   To be exact, they can block the production of the protein PCSK9, which inhibits the regulation of cholesterol.   Robert Metcalfe, the inventor of Ethernet, is a backer.
  • Prof. Darrell Irvine notes that the long-term survival rate of cancer used to be really bad, but with T-cell immunotherapy it got up to 25%.  That’s still pretty awful, and the reason is that the cancer can use the body’s own defenses against invaders to attack the introduced T-cells.  He has found a way to attach particles of drugs to the outside of the T-cells, and release them in the environment of the tumor to slow down the attackers.
  • Prof. Jacquin Niles says that the first successful anti-malarial drug, chloroquine, has become useless as the bacteria adapted to it, and the second, artemisinin, is losing too. The disease kills 700,000 people a year, mostly children in Africa.  He’s now going after the bacterium’s genome one gene at a time, clipping them out individually with CRISPR to see which ones the drugs are actually responding to.  Sponsored by the Gates Foundation.
  • Prof. Eric Alm is studying the micro-biome, the set of bacterial species that live in our guts and have mysterious influences over us.  We can now sequence them all and so see if key species are missing.  Problems here could be associated with multiple sclerosis and even autism.  It’s another job for neural nets!   It’s possible to transplant the species if we could just figure out what they do.

And finally, Prof. Angela Belcher talked about doing actual machine fabrication with biological methods.   She notes that abalones manage to produce incredibly tough shells using just the elements they can extract from seawater.  Shouldn’t we be able to make finely-layered materials using similar techniques?

One big accomplishment of her lab was to fabricate the electrodes for a lithium-ion battery using a mat of viruses coated with iron phosphate.   Paper here – Fabricating Genetically Engineered High-Power Lithium Ion Batteries Using Multiple Virus Genes. Actual battery here:

Angela Belcher holds a display of the virus-built battery she helped engineer. The battery -- the silver-colored disc -- is being used to power an LED.

The silver disk is the virus-built battery, and it’s powering an LED. Photo Donna Coveney. Click for story.

They adjusted the genes of the virus so that it would create a protein that could hold onto a carbon nanotube.   The nanotubes are only 1 nm wide and 500 nm long, so nothing else can handle them except a scanning tunneling microscope.   Here they make a billion viruses to pick up a billion  tubes at a time.  Then they dunk them in iron phosphate to actually form the electrode to grab the lithium ions, and the nanotubes make the overall material conductive.  The whole process can be done with common materials at room temperature.   They used the M13 bacteriophage virus, which is otherwise harmless.

What’s even wilder is that they can evolve these capabilities through un-natural selection.   Give each virus a different genome and see if they attach to something on a substrate.   If they don’t, wash them away, then repeat the process with the survivors.   You can try billions of variations after a few cycles.   They’re now trying this on particles of lead.  The surface of a lead crystal has a certain pattern of charges that a protein could lock onto.   Evolve those viruses in this hyper-accelerated way, and you have a way to remove lead from drinking water.   Build a filter out of a mass of these viruses, and pour stuff through it.   Make sure that the viruses themselves can be destroyed in another step!

Overall, what MIT is doing is creating a new field of engineering.   To the usual set of electrical, chemical, mechanical, and civil engineering, they’re adding a new one: biological engineering.  They call it Course 20.  It’s now moving beyond medicine and into actual machine manufacture.    People have used the bio-robots called yeast to make beer and soy sauce for millenia, but now we’ll build all sorts of other things with them.    It’s just the sort of breakthrough that alumni are proud to see their alma mater working on.

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