themselves.

The idea behind the new targeted has tested a similar approach in babies with a into separate collaborations with researchers
approaches is to eradicate specific stem cells genetic disorder that cripples the immune sys- developing gene therapies to treat blood dis-
to make room for transplanted cells without tem. The researchers, in a collaboration that orders such as β-thalassaemia and sickle-cell
the side effects of existing treatments, which includes the firm Amgen of Thousand Oaks, disease (see page 22).
destroy bone marrow cells indiscriminately. California, used a third antibody that targets And data are accumulating to show that
Physicians currently rely on full-body radi- c-Kit. The team found that transplanted stem some people with type 1 diabetes, systemic
ation or treatment with toxic, DNA-damaging cells, in this case from donors who did not have scleroderma and other autoimmune disor-
chemotherapy drugs to kill existing blood the disease, successfully took hold in the bone ders can enter long-lasting remission if the
stem cells and clear the way for the trans- marrow of four out of six of the babies. mature immune cells in their bone marrow
planted cells to repopulate the marrow. That are wiped out and replaced with an infusion
preparation kills not only blood stem cells, but Expanding market of their own blood stem cells (E. Snarski et al.
also a host of other cells in the marrow. This can These developments come as the potential Bone Marrow Transpl. 51, 398–402; 2016;
cause infertility, seed cancers that occur later market for blood-stem-cell transplants is K. M. Sullivan et al. N. Engl. J. Med. 378, 35–47;
in life, and severely compromise the immune expanding, says Mani Foroohar, an analyst 2018). The procedure is thought to reset the
system, leading to lengthy hospital stays. at SVB Leerink investment bank in Boston, immune system by eradicating cells that are
“It’s really prohibitive for patients,” says Massachusetts. attacking the body’s own tissue, says Keith
David Scadden, a stem-cell biologist at Har- Some gene therapies, such as one recently Sullivan, a stem-cell transplant physician at
vard University in Cambridge, Massachusetts. approved by European regulators to treat a Duke University in Durham, North Carolina.
“This technology just won’t be adopted unless genetic immune disorder called ADA-SCID, Sullivan says that the early data from
we really change the whole dynamic.” use a version of the technique. They remove Shizuru and others are intriguing, and that
the patient’s blood stem cells, then geneti- he has begun discussions to collaborate with
Stem-cell hotel cally modify them so that they are free of the researchers in the field. “The train is moving
One way to think about stem-cell transplants disorder before infusing them back into the now,” he says. “The question is, how do we do
is that the bone marrow is a hotel whose owner body. Magenta and Forty Seven have entered this in the right way?”
wants to evict some guests, says Jens-Peter
Volkmer, vice-president of research at Forty
Seven, a biotechnology company in Menlo

CARBON DIOXIDE-EATING
Park, California. Current treatments blow up
the whole hotel, he says. “Then everybody’s

BACTERIA OFFER HOPE

dead, including all of these critical compo-
nents that you need to protect the patient

FOR GREEN PRODUCTION

from infection.” The latest approaches allow
the owner to tell specific guests to leave — by
targeting sets of cells in the bone marrow,
rather than killing them all, Volkmer says.
At the haematology meeting, which begins Lab workhorse E. coli engineered to make nutrients
on 7 December, researchers from Forty Seven
will present the results of studies that tested from greenhouse gas rather than from sugars.
a combination of two antibodies in monkeys.
By Ewen Callaway

E
One antibody blocks the activity of a molecule Plants and photosynthetic cyanobacteria —
called c-Kit, which is found on blood stem cells aquatic microbes that produce oxygen — use
and is vital to their function; the other inhibits scherichia coli is on a diet. Researchers the energy from light to transform, or fix, CO2
a protein called CD47, which is found on some have created a strain of the model into the carbon-containing building blocks
immune cells. Inhibiting CD47 allows those bacterium — known as E. coli for short of life, including DNA, proteins and fats. But
immune cells to sweep up the stem cells tar- — that grows by consuming carbon these organisms can be hard to genetically
geted by the c-Kit antibody, making way for dioxide instead of sugars or other modify, which has slowed efforts to turn them
new cells. organic molecules. into biological factories.
In the tests, the combination reduced the The achievement is a milestone, say By contrast, E. coli is relatively easy to engi-
number of blood stem cells in bone marrow. scientists, because it drastically alters the neer, and its fast growth means that changes
But the team has not yet demonstrated that inner workings of one of biology’s most pop-
the treatment clears out enough old cells to ular model organisms. And, in the future, “After about 200 days,
allow transplanted cells to flourish. CO2-eating E. coli could be used to make
Another company, Magenta Therapeutics of organic carbon molecules for biofuels or to
cells capable of using CO2
Cambridge, Massachusetts, has collaborated produce food. as their only carbon source
with researchers at the US National Institutes Products made in this way would have lower emerged.”
of Health to test a different antibody, which emissions than those made using conventional
binds to c-Kit and then releases a toxin to kill production methods, and could potentially
the blood stem cell that produced the protein. remove the gas from the air. The work was can be quickly tested and tweaked to optimize
Data from studies in mice and one monkey sug- published on 27 November (S. Gleizer et al. genetic alterations. But the bacterium pre-
gest that this can kill off enough stem cells in Cell 179, 1255–1263; 2019). fers to grow on sugars such as glucose — and
the bone marrow for transplanted cells to “It’s like a metabolic heart transplanta- instead of consuming CO2, it emits the gas as
thrive — without destroying other cells such tion,” says Tobias Erb, a biochemist and waste.
as immune cells. synthetic biologist at the Max Planck Institute Ron Milo, a systems biologist at the
And a team led by transplant physician Judith for Terrestrial Microbiology in Marburg, Weizmann Institute of Science in Rehovot,
Shizuru at Stanford University in California Germany, who wasn’t involved in the study. Israel, and his team have spent the past

Nature | Vol 576 | 5 December 2019 | 19

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News in focus
decade overhauling E. coli’s diet. In 2016, they says Milo. Compared with normal E. coli, which
created a strain that consumed CO2, but the can double in number every 20 minutes, the
compound accounted for only a fraction of autotrophic E. coli are laggards, dividing every
the organism’s carbon intake — the rest came 18 hours when grown in an atmosphere that is
from an organic compound that the bacteria 10% CO2. They are not able to subsist without
were fed, called pyruvate (N. Antonovsky et al. sugar on atmospheric levels of CO2 — currently
Cell 166, 115–125; 2016). 0.041%.

Gas diet A long way to go

In the latest work, Milo and his team used a mix Milo and his team hope to make their bacteria
of genetic engineering and laboratory evolu- grow faster and live on lower levels of CO2.
tion to create a strain of E. coli that can get all of They are also trying to understand how the
its carbon from CO2. First, they gave the bacte- E. coli evolved to eat CO2: changes in just
rium genes that encode a pair of enzymes that 11 genes seem to have allowed the switch,
allow photosynthetic organisms to convert and researchers are now working on finding
CO2 into organic carbon. out how.
Plants and cyanobacteria power this con- The work is a “milestone” and shows the

STEVE GSCHMEISSNER/SPL
version with light, but that wasn’t feasible for power of melding engineering and evolution
E. coli. Instead, Milo’s team inserted a gene to improve natural processes, says Cheryl
that lets the bacterium glean energy from an Kerfeld, a bioengineer at Michigan State
organic molecule called formate. University in East Lansing.
Even with these additions, the bacterium Researchers have already used E. coli to
refused to swap its sugar meals for CO2. To fur- The model bacterium Escherichia coli. make synthetic versions of useful chemicals
ther tweak the strain, the researchers cultured such as insulin and human growth hormone.
successive generations of the modified E. coli CO2 as their only carbon source emerged. And Milo says that his team’s work could expand
for a year, giving them only minute quantities after 300 days, these bacteria grew faster in the products the bacteria can make to include
of sugar, and CO2 at concentrations about the lab conditions than did those that could renewable fuels, food and other substances.
250 times those in Earth’s atmosphere. not consume CO2. But he doesn’t see this happening soon.
They hoped that the bacteria would evolve The CO2-eating, or autotrophic, E. coli “This is a proof-of-concept paper,” agrees
mutations to adapt to this new diet. After strains can still grow on sugar — and would use Erb. “It will take a couple years until we see this
about 200 days, the first cells capable of using that source of fuel over CO2 given the choice, organism applied.”
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