[Ip-health] The Economist: Who won this year’s Nobel science prizes? The laureates proved black holes are real, created a new form of gene editing and identified the hepatitis C virus

Thiru Balasubramaniam thiru at keionline.org
Fri Oct 9 09:43:46 PDT 2020


Science & technology
Oct 8th 2020 edition

Who won this year’s Nobel science prizes?

The laureates proved black holes are real, created a new form of gene
editing and identified the hepatitis C virus

October’s first week is a nervous time for scientists with serious
accomplishments under their belts—for this is when the phone might ring
from Stockholm. Those who give out the Nobel science prizes (the Karolinska
Institute for the physiology or medicine award, and Sweden’s Royal Academy
of Science for the awards in physics and chemistry) are known neither for
offering the winners more than an hour or two’s notice of the public
announcement of their success, nor for respecting time zones. New laureates
in North America receive the news in the dead of night. That, though, is
normally reckoned a small price to pay for what is still seen as science’s
most prestigious honour.

Britain being in a more convenient time zone from the Swedish point of
view, Sir Roger Penrose, of Oxford University, was not actually asleep when
his own phone rang. But he was, he says, in the shower. He was one of three
winners of the physics prize, the others being Andrea Ghez and Reinhard
Genzel, of the University of California’s Los Angeles and Berkeley campuses
respectively. Their prize was for the theoretical explanation and
subsequent discovery of some of the strangest objects in the universe:
black holes.


Chase to the cut

As is often the way, the chemistry prize went for a discovery that might
equally well have been handed out for medicine—crispr-Cas9 gene editing.
The winners were Emmanuelle Charpentier of the Max Planck unit for the
science of pathogens, in Berlin, and Jennifer Doudna of the University of
California, Berkeley.

crispr-Cas9 is derived from a bacterial defence mechanism that snips small
sequences of dna from viral interlopers and copies them into a bacterium’s
own genome, thus creating a scrapbook by which to recognise such
aggressors, should they come again. The laureates’ prize is not, though,
for the mere discovery of a novel bacterial immune system. It is for the
adaptation of that discovery into the most important gene-editing tool yet
invented—one that is already helping to design disease-resistant crops and
new therapies for cancer, and which may, perhaps, end hereditary disease in
human beings.

If an organism’s collective dna can be thought of as the book of its life,
crispr-Cas9 allows for any specific sequence of words within that book to
be identified, selected, removed and replaced. This is done by creating a
molecule called a guide rna, which matches a target dna sequence, and
pairing it with an enzyme, Cas9, that is capable of snipping the dna helix
at this point. Then, if so desired, a new piece of dna can be inserted.

The laureates’ path to Stockholm began at a café in Puerto Rico in 2011.
That was when Dr Charpentier, who had discovered intriguing and unexplained
rna fragments in a bacterium, engineered a meeting with Dr Doudna, an
expert in the dna-snipping capability of Cas proteins. Since this
collaboration bore fruit in 2012, progress has been rapid. By February 2013
Feng Zhang of the Broad Institute in Cambridge, Massachusetts and George
Church of Harvard Medical School had independently demonstrated the
technique’s effectiveness in mouse and human genomes, paving the way for
the treatment of human diseases. Clinical trials are now under way to test
its power against sickle-cell anaemia and certain cancers, with animal
experiments showing promising results in the treatment of muscular

There has also been controversy. In 2018 He Jiankui of the Southern
University of Science and Technology, in Shenzhen, China, announced the
birth of twin girls whose embryos he had edited with the help of
crispr-Cas9. Dr He’s stated goal was to induce immunity to hiv, by
disabling the gene for a protein which that virus uses to gain admission to
cells. This was too much for the authorities. Even ignoring the issues of
consent involved when a procedure is carried out on an embryo, making
genetic edits so early in life means that they will be incorporated into
germ cells, and thus passed down the generations. That raises serious
ethical questions, and what Dr He did was declared illegal by the Chinese
government. Dr He is now in prison.

Nor is germ-line editing the only controversy surrounding crispr-Cas9. A
further complication concerns who gets the patents that will monetise it.
The University of California and the Broad have been involved for years in
a legal battle over the matter. By giving the prize to Dr Doudna and Dr
Charpentier the Royal Academy of Science may have put its thumb on the
scales. In picking them it has also, for the first time, awarded a Nobel
science prize to an all-female group. Dr Charpentier, via a phone link to
the room where the announcement was made, said “I hope this provides a
positive message to young girls. Women in science can also be awarded
prizes. But more importantly, women in science can also have an impact.”

Regardless of which category it truly fits into, the creation of
crispr-Cas9 was a high-end piece of technowizardy. The actual prize for
medicine, however, went for a piece of old-fashioned medical detective
work—the identification of hepatitis C, a virus that causes
life-threatening liver infections and is passed on by exposure to
contaminated blood. Though other widespread diseases, such as malaria and
hiv/aids, gain more attention, the World Health Organisation (who) reckons
that around 70m people are infected with hep C and that it kills 400,000
people a year. Hep C has also, in the past, turned the business of blood
transfusion into a lottery, since there was no way to tell whether a
particular batch of blood harboured it. That this is no longer the case is,
in no small measure, thanks to the work of this year’s laureates—Harvey
Alter, Michael Houghton and Charles Rice.

Blood simple

Dr Alter’s work came first. In the 1960s he was a colleague of Baruch
Blumberg, who discovered the hepatitis B virus (for which he won a Nobel
prize in 1976). Hepatitis viruses are labelled, in order of discovery, by
letters of the alphabet. “A”, a waterborne pathogen, causes an acute
infection that passes after a few weeks and induces subsequent immunity.
The effects of “B” and “C”, though, are chronic and may result eventually
in cirrhosis and cancer. Blumberg’s discovery led him to a vaccine for hep
B, and also meant that blood intended for transfusion could be screened.
But it became apparent that such screened blood still sometimes caused
hepatitis, albeit at lower rates. Since hep A was also being screened for
by this time, that suggested a third virus awaited discovery.

In 1978 Dr Alter, then working at America’s National Institutes of Health,
proved this was true by injecting into chimpanzees blood from recipients of
transfusions screened for the known viruses who had nevertheless developed
hepatitis. These animals sometimes then went on to develop the illness. It
took until 1989 to clone the new virus. That was done by Dr Houghton, who
was then working at Chiron, a Californian biotechnology firm subsequently
bought by Novartis, a Swiss pharmaceutical giant.

Dr Houghton amplified viral genetic material drawn randomly from
chimpanzees infected with the as-yet-unidentified virus and tested this
against antibodies from infected humans. Antibodies are proteins crafted by
the immune system to stick specifically to parts of particular pathogens.
By looking at which chimpanzee-derived material the antibodies in question
attached themselves to, Dr Houghton was able to isolate the virus and
identify it as a type of flavivirus, a group that also includes yellow
fever and dengue. He also thus provided a way of screening blood intended
for transfusion.

Dr Rice, working at Washington University, in St Louis, Missouri,
eliminated lingering uncertainties about whether the flavivirus Dr Houghton
had identified was the sole cause of hep C. Attempts to use cloned,
purified versions of it to infect chimpanzees had not worked, leading to
doubts about whether it was acting alone. Dr Rice identified part of the
viral genome which looked crucial to the process of infection, but was
highly mutable. He suspected that this mutability was hindering successful
infection in the laboratory, and was able to eliminate it by genetic
engineering. The stabilised virus was, indeed, infectious to chimps.

The consequence of all this is that blood for transfusion can now be
screened routinely for hep C, and drugs to treat it have now been
developed. Unfortunately, this has not stopped the march of the illness.
Those in rich countries have benefited. Deaths in Britain, for example,
fell by 16% between 2015 and 2017. But the wider picture is grim. Some
countries, such as Egypt, have recently done well. Others, less so.

One reason is that, besides transfusion, hep C is spread by drug users
sharing needles. It can also be spread sexually. This stigmatises it in the
eyes of some. And unlike hiv/aids, which spreads in similar ways but
quickly developed a political lobby to find a treatment once it was
discovered, no one spoke up at the beginning for those suffering from the
effects of hep C.

That is starting to change. In 2016 the who published a strategy for the
elimination of all forms of hepatitis. The tools are there to do this.
Whether the will to use them also exists remains to be seen.■

This article appeared in the Science & technology section of the print
edition under the headline "They walked in looking like dynamite"

Thiru Balasubramaniam
Geneva Representative
Knowledge Ecology International
41 22 791 6727
thiru at keionline.org

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