Lab Escape Theory of SARS-CoV-2 Origin Gaining Scientific Support

Several scientists as well as ongoing scientific research, including studies published on pre-peer review websites, are backing the idea that SARS-CoV-2 began in a lab. Scientists cite several reasons for blaming a lab creation for the pandemic....

May 28, 2020




“We can’t exclude the possibility that this came from a laboratory experiment rather than from an animal” – Prof Nikolai Petrovsky

Several scientists as well as ongoing scientific research, including studies published on pre-peer review websites, are backing the idea that SARS-CoV-2 began in a lab.

Scientists cite several reasons for blaming a lab creation for the pandemic. Even Chinese scientists are walking back their initial finger-pointing at a local “wet” market as the source of the virus.

The possibility that SARS-CoV-2 is a human-manipulated virus that escaped from a lab has been flagged up by a whole series of scientists, such as Prof Richard Ebright, Prof Stuart Newman, Dr Michael Antoniou, Dr Jonathan Latham, Yuri Deigin, Dr Billy Zhang, and Prof Jonathan J. Couey.

Now it is gaining further scientific support in the form of two papers, recently posted on academically established pre-peer review websites. Although these studies have not yet been peer-reviewed, they are being taken seriously by the scientific community, which has opened up a lively discussion on social media.

The first study, led by Dr Alina Chan at the Broad Institute, MIT (USA), strongly challenges the much promoted narrative that the virus jumped from animals to humans at the Huanan seafood and wildlife market in Wuhan, China.

The researchers compared SARS-CoV-2 to the earlier SARS virus, SARS-CoV, which caused a human epidemic in 2003. They found that by the time SARS-CoV-2 was first officially announced and its genetic sequence reported in late 2019, it was already pre-adapted to human transmission, to an extent similar to late epidemic SARS-CoV. This is very different from how SARS-CoV first emerged. That virus was initially far less well adapted to infecting humans and had to acquire many mutations gained though many rounds of infectious cycles to reach peak infectivity. This type of progressive adaptation (mutation and selection) is exactly what is expected and known to happen in animal to human virus disease transmission. But SARS-CoV-2, even at very early stages of its detection in humans, was already highly adapted for human infectivity. In other words, no sufficiently similar natural “parent” animal virus or, in the researchers’ words, “branches of evolution stemming from a less well-adapted human SARS-CoV-2-like virus” have been found.

Casting further doubt on the “zoonosis” (jump from animal to human) theory of the virus’s origin is that samples taken from the Huanan market in Wuhan were found to contain viruses that were genetically identical to human SARS-CoV-2. According to Dr Chan, “This makes it unlikely for the Huanan market isolates to have come from an intermediate animal host; likely from SARS2-infected humans who visited the market.”

Interestingly, just in the last few days Chinese scientists have themselves thrown cold water on the “wet market” theory. According to the Wall Street Journal, "China’s top epidemiologist said Tuesday that testing of samples from...[the wet market]...failed to show links between animals being sold there and the pathogen." As all pandemic-related communications from scientists in China are now centrally vetted, we can conclude that the Huanan market theory is being walked back at an official level because of the lack of supporting evidence.

Indeed, on 27 May the Chinese government came up with another theory for the virus’s emergence. The Huanan market is now described as “more of a victim rather than the origin” of SARS-CoV-2 and the the virus is now claimed to have “multiple origins” – a suitably vague term that says nothing about laboratory escapes.

Lab escape theory “should be considered”

Alina Chan and colleagues say, "The sudden appearance of a highly infectious SARS-CoV-2 presents a major cause for concern that should motivate stronger international efforts to identify the source and prevent near future re-emergence." In this context they conclude that the possibility of a lab escape “should be considered regardless of how likely or unlikely”.

In GMWatch’s view, Dr Chan’s research suggests one of three potential origin scenarios:
1) SARS-CoV-2 has a natural origin in animals. If this is the case, it must have been circulating in humans in Wuhan long before the Chinese government alerted the international authorities to the COVID-19 epidemic, thus giving the animal virus the time needed to adapt to humans, as was seen with SARS-CoV in the 2003 epidemic.
2) SARS-CoV-2 is a natural animal-derived virus that has been studied in a laboratory for human infectivity for a considerable period of time, during which it acquired mutations that make it highly infectious to humans. The human-adapted virus then escaped from the lab that was studying it, with the Wuhan Institute of Virology (WIV) being a prime candidate.
3) SARS-CoV-2 is a genetically engineered virus that escaped from a lab that constructed it, such as the WIV.

Interestingly, however, the researchers pre-emptively close off the third option. They define the potential lab-origin virus as “non-genetically engineered”, even though their paper presents no evidence that such a virus could not have been genetically engineered. Given the long history of genetic engineering of coronaviruses at the WIV, this is an unwarranted assumption.

GMWatch pointed out to Alina Chan on Twitter that based on her research, the virus could be GM, or not. Dr Chan conceded that this was the case – “That’s right” – adding that “there is no direct evidence for any particular origin scenario”. Her latter comment is correct, but her admission that the virus could be GM shows that her claim in the paper that it is non-genetically engineered is inaccurate and requires correction in any final published paper.

Another Twitter commentator responded to our tweet by citing data from biotech entrepreneur Yuri Deigin’s blog post, which lays out strong evidence in support of the virus being genetically engineered.

Human intervention possible

The other paper pointing to a possible lab escape is more forthright about the possibility of human intervention. The paper is authored by a team led by Nikolai Petrovsky, a vaccine developer and a professor at the College of Medicine and Public Health at Flinders University in Adelaide, Australia. Using cutting edge computer molecular modelling tools, the researchers conclude that SARS-CoV-2 contains unique properties that mean it could have been cultured and selected in the laboratory to increase human infectivity.

Prof Petrovsky said his team considers that human manipulation is plausible because of the unmatched ability of the virus’s protruding spike protein to infect human cells. The virus’s ability to bind to human cells “far exceeds” its ability to infect other animals, he said. He added, “This, plus the fact that no corresponding virus has been found to exist in nature, leads to the possibility that COVID-19 is a human-created virus. It is therefore entirely plausible that the virus was created in the biosecurity facility in Wuhan [WIV] by selection on cells expressing human ACE2 [receptor], a laboratory that was known to be cultivating exotic bat coronaviruses at the time.”

Prof Petrovsky told Sky News that he also doesn’t exclude the natural origin theory: “The two possibilities which I think are both still open is that it was a chance transmission of a virus from an as yet unidentified animal to human. The other possibility is that it was an accidental release of the virus from a laboratory. Certainly we can’t exclude the possibility that this came from a laboratory experiment rather than from an animal. They are both open possibilities.”

Genetic engineering the quicker way to human infectivity

Commenting on Prof Petrovsky’s conclusion that SARS-CoV-2 could have originated from culture of a wild virus and selection in human cells, the London-based molecular geneticist Dr Michael Antoniou agreed that this scenario was plausible: “You can certainly develop a human-infective virus like SARS-CoV-2 by repeatedly passing a wild bat virus through human cells, in the way that Prof Petrovsky describes. You culture human cells with the virus, allowing the virus to replicate, and harvest the resulting viruses. This selects for the most human-infective viruses, which you use to re-infect more cells. By going through successive rounds of this process, you are gradually selecting for viruses that have acquired mutations leading to enhancement of human infectivity. Eventually you end up with a virus that is optimized for human infectivity.”

However, Dr Antoniou added that there are far quicker and more efficient ways to achieve this aim.

For example, if you start with little information about what your human-infective virus looks like, you can genetically engineer a large number of SARS-CoV spike protein variants within phages. Phages are viruses that can infect bacteria. Phages can be genetically engineered to express on their exterior coat the CoV spike protein with a different variant of the receptor binding domain (RBD) – the part of the spike protein that allows the virus to bind to the ACE2 protein on human cell surfaces and thus enables infection to take place. This collection of phage variants with different RBDs is called a “phage display library”. The “library” of variants is then cultured with human cells in order to select for those phages with spike protein variants that bind to the ACE2 receptor.

Then the DNA is extracted from the phage with the best-binding spike protein and sequenced. Based on the sequence, a whole virus optimized for human infectivity can be synthesized.

Alternatively, Dr Antoniou explained, if you start with some information, as is likely with a group of researchers experienced in coronavirus gain-of-function research, there is an even quicker way to create a human-infective virus. Given that past research indicates that the nature of the spike protein alone doesn’t determine infectivity, it seems sensible to generate a library of spike mutant proteins directly within a whole coronavirus, which would also contain any other components necessary for infectivity.

In this case, you would take a DNA clone of a coronavirus that you know to be close to human infectivity, based on the sequence of its RBD. (Manipulation of DNA clones of coronaviruses is the standard procedure used to generate mutant viruses, including chimeras, in gain-of-function experiments, such as those carried out by scientists at the University of North Carolina and the Wuhan Institute of Virology.) You would then use the genetic engineering technique of DNA synthesis to generate a large number of randomly mutated versions of the spike protein RBD. The RBD mutations that you engineer could be more narrowly targeted by focusing on those regions encoding the amino acids whose nature and positions you know to be most critical for docking onto the human ACE2 receptor. The mutant versions of the RBD would then be selected for strong binding to the ACE2 receptor and consequently high infectivity of human cells.

Both methods described above would not leave any “signature” of genetic engineering. That’s an important consideration, given that Prof Petrovsky believes that genetic engineering was not involved in the development of SARS-CoV-2 due to the absence of such a signature.

Genetic engineering likely

In GMWatch’s view, to bypass the efficient genetic engineering-based methods described by Dr Antoniou in favour of the more laborious culture and selection-only method suggested by Prof Petrovsky would seem a curious decision for any laboratory committed to investigating coronavirus gain-of-function, such as the WIV.

The conclusions that we draw from these two new papers and Dr Antoniou’s input are that the “zoonosis” theory of SARS-CoV-2’s origin looks increasingly open to question, that the lab escape theory appears to be a solidly based scenario and, if that is what happened, genetic engineering is highly likely to have played a part in the development of the virus.

Report by Claire Robinson

SOURCE: GM Watch May 28, 2020
https://www.gmwatch.org/en/news/latest-news/19412-lab-escape-theory-of-sars-cov-2-origin-gaining-scientific-support

After 6 Months, Important Mysteries About Coronavirus Endure

In the time since the world’s scientists and public health officials first became widely aware of the new coronavirus in January, they’ve had six months to learn about it.

 

The New York Times  2 June 2020

 

12 hrs ago

They’ve reached many conclusions about the virus and the illness it causes, from the importance of wearing masks to contain it, to the unusual range of symptoms it provokes.

But there are major gaps in scientific knowledge about the virus. In the half year that journalists of the health and science desk of The Times have been reporting on Sars-CoV-2, we have identified some of the enduring uncertainties. How scientists resolve some of these mysteries will shape our future with the coronavirus.

How many people have been infected.

One of the epidemic’s great unknowns is how many Americans have been infected so far.

Only about 1.9 million Americans had tested positive as of May 28, according to the Centers for Disease Control and Prevention — or perhaps only about 1.7 million according to the Johns Hopkins Center for Health Security, which produces a frequently cited map of world cases.

Statisticians believe the actual number of cases is higher, but it is not clear by how much.

They have more confidence in the accuracy of data produced by states that do the most testing. On that score, New York is a leader; it has tested about 9.6 percent of its population, which is almost double the national average. (Rhode Island tested 13 percent of its people, beating New York, but its population is small.)

New York has also done tens of thousands of antibody tests for surveillance purposes. On May 22, Gov. Andrew Cuomo announced that, according to these tests, about a fifth of all New York City residents have had the virus, as had about 27 percent of thousands of black and Hispanic New Yorkers who were tested at their local churches.

© Jens Mortensen for The New York TimesIf that same pattern were assumed to hold in other hard-hit big cities like Chicago, New Orleans, Detroit and Miami, it is likely that somewhere between 3 and 4 million urban Americans were infected.

Even if that figure was doubled or tripled — which is probably generous — to account for Americans infected all around the country before the lockdowns, that would still be only 9 to 12 million people.

That is in line with the low end of estimates made in mid-April, before antibody testing began; different modelers predicted then that between 3 and 10 percent of the country was infected.

In any case, since this is a country of 330 million, a mere 10 million or even 20 million infected would be a drop in the bucket. As the country comes out of lockdown, the vast majority of Americans remain vulnerable to the virus.

Nor will the country be able to spot all of those who get it. The C.D.C.’s “best estimate,” according to the pandemic scenarios it issued May 22, is that about 35 percent of those infected have no symptoms.

Currently, about 21,000 Americans are getting infected each day. If a third of them show no symptoms, almost 210,000 “silent spreaders” are created each month.

It seems impossible to imagine that any contact-tracing program, no matter how large, will be able to keep up with that.

The amount of virus it takes to make you sick.

Here’s what we can say for sure about the minimum number of viral particles it takes to seed a coronavirus infection: The number is somewhere between one and one million.

© Jens Mortensen for The New York TimesIf you push scientists harder, they might offer a slightly smaller range of a few hundred to a few thousand — and some might even bravely throw out an estimate in the high hundreds, based on what they have learned about the behavior of the coronavirus that caused the 2002-03 SARS epidemic.

But the bottom line is that no one will know for sure until more research is completed.

“It’s very unsatisfying to tell people, ‘Oh we don’t know,’” said Angela Rasmussen, a virologist at Columbia University in New York. “People do have a lot of questions about this.”

It’s difficult to say anything definitive about the coronavirus because it behaves like an influenza virus in how easily it is transmitted, and in that people can pass it on even when they don’t seem sick. But its structure, origin in bats and overall symptoms are similar to those of its cousin coronaviruses.

So scientists cannot say whether touching a surface with a smidgen of virus or breathing air with a few droplets exhaled by a sick person will make you ill. But it is safe to say exposure to more of the coronavirus is more likely to cause infection, and also to lead to more severe symptoms. That’s why it’s important to avoid crowded indoor spaces, wear masks and wash your hands. Each of those steps can decrease your chances of being exposed to large amounts of virus.

Why some people get so much sicker than others.

Covid-19 is a mercurial disease. While some people experience only mild, fleeting symptoms, others are knocked over with a severe flulike illness that can last several weeks. A minority of patients develop life-threatening complications. Death can ensue.

Why do some people sail through the illness, and others develop the severe inflammation and lung damage that are hallmarks of the disease? It is one of the great mysteries of Covid-19.

Experts say the patient’s immune response to the viral infection determines the severity of the illness. If the immune system goes into overdrive, it can trigger a cascade of harmful effects, injuring the lungs and other organs.

Immune function declines with age, and elderly people with Covid-19 are among the most vulnerable to poor outcomes, as are those with chronic health conditions like high blood pressure, diabetes and cardiovascular disease. Obesity, which affects 4 in 10 American adults, also appears to exacerbate the illness.

Men are at greater risk for critical illness and death, a sex disparity that may be explained by women’s more robust immune systems, scientists say.

Generally speaking, patients get sicker faster if they are exposed to a large dose of the virus when they are first infected, said Dr. William Schaffner, an infectious disease specialist at Vanderbilt University.

Much scientific inquiry has focused on the role of a receptor called angiotensin-converting enzyme 2, or ACE2, which is the entry way for coronaviruses into the cells. The receptor is found on the outer surfaces of cells in the lungs, blood vessels, intestines and other organs, as well as in the back of the throat and high up in the nasal passage.

When the pandemic started, there was concern that people taking blood pressure medications like ACE inhibitors could be at greater risk from the coronavirus, but so far studies have not found that to be the case, and doctors are urging patients to continue their medications.

Though the SARS-CoV-2 virus attaches to the receptor in order to penetrate cells, ACE2 also helps regulate blood pressure and inflammation. Some scientists have suggested that children may be less susceptible to infection with Covid-19 because they have fewer of these receptors. ACE2 is also regulated differently in men and women, according to scientists who study sex differences in medicine, and men tend to develop hypertension, or high blood pressure, at younger ages than women. But much is still unknown.

© Jens Mortensen for The New York Times“ACE2 can play two very critical roles, getting the virus into the cell, but also modulating some of the damage that takes place in the blood vessels and the lungs,” said Dr. Ankit B. Patel, a nephrologist at Brigham and Women’s Hospital in Boston. “So it’s a double-edged sword in a sense, and that’s made the whole story all the more complicated.”

The role of children in spreading the virus.

There are many crucial unresolved questions about children and Covid-19. Finding the answers is not only important for them and their families, but for society at large, as communities plan to reopen schools, day care centers, playgrounds and other places children frequent.

One puzzle is what role children play in spreading the virus. They seem less likely to become seriously ill than adults, making up about 2 percent of confirmed American coronavirus cases. There are different theories about whether that is because children are less likely to become infected to begin with, or whether the virus infects them just as easily but mostly causes few or no symptoms.

Either way, a growing body of evidence suggests that infected children can transmit the virus, possibly as easily as adults. And one recent study suggests that when children attend school, they come in contact with three times as many people as average adults do, providing more opportunities for children to become infected and infect others.

Although far fewer children than adults have experienced severe symptoms, some children have become devastatingly ill and there have been at least 20 deaths of children from Covid-19 in the United States and elsewhere. Reports from hospitals suggest that the children most vulnerable to the respiratory failure adults develop are those who already have a serious medical condition. Some studies also suggest that infants and preschoolers may be more vulnerable than older children.

But a small number of other children, including teenagers, who did not have any symptoms when they were first infected, have developed a newly-identified inflammatory syndrome that can cause serious heart problems. The syndrome, which seems to occur weeks after infection and to result from a revved-up immune response to the virus, has been reported Europe and throughout the United States and has caused several deaths. Doctors are urgently trying to understand what causes the syndrome, why it afflicts some children and not others, and how to best treat or prevent it.

When or where the new coronavirus started spreading.

The notion of a single patient zero is both theatrical and real: In any new epidemic, some unlucky soul seeds the first infection, several links of which are fated to seed chains of their own and spark a viral Big Bang.

By analyzing the genetic material of people who test positive, scientists can trace the lineage of each virus back to a common ancestor, and often to an individual carrier. The first confirmed coronavirus case in the United States was a man who landed at Seattle-Tacoma Airport on Jan. 15, from China. Other introductions came in February, and scientists are now closing in on who, exactly, sparked the outbreak in Washington State.

New York confirmed its first case on March 1, and by that time there were already thousands of infected people walking around, for a week or more. Scientist have found genetic signatures on the viruses studied so far that link them to Europe, likely brought in by some of the millions of people arriving in New York in February, and it is likely that there were multiple introductions that spread widely: patients zero, plural.

The first infected arrivals in a community are not necessarily the ones who light the fuse. In a report published last week, genetic scientists argued that infected people were among both Americans and Europeans in January, but that most of those viruses fizzled out. And French doctors recently reported that a respiratory sample from a man hospitalized near Paris, in late December, tested positive. That virus, too, likely died out. France’s outbreak did not start until many weeks later.

The world’s patient zero, in China, began infecting others in the late fall of last year, the evidence thus far suggests. An analysis of the first 41 confirmed cases, all in people who had visited the same seafood market in Wuhan, indicates that the first hospital admission was on Dec. 16, 2019. The patient first noticed symptoms on Dec. 1, so the infection dates back earlier. Several scientists have estimated that the first outbreak began in late or mid-November, and have inferred a probable common viral ancestor, though additional virus samples could change the picture.

The level of detective work required to find the actual patient zero might be steeper than it appears. At least one genetic scientist has argued that the virus could have first infected humans — likely from a pangolin — well before last fall, in a form that did not cause sickness. It then evolved its pathogenic features over time, while circulating. If that’s the case, the question “Who came first?” may go without a conclusive answer for some time, perhaps for good.

How long you’ll be immune after infection.

Are people infected with the coronavirus protected from further infection? And, if yes, for how long?

The answers to these questions have broad implications for reopening the economy and allowing the public to live with less fear of infection in the short term — and for the effectiveness of vaccines in the long term.

Scientists have made steady, if incremental, progress in getting to the answers. When the body encounters any virus, it typically makes antibodies, some of which are powerful enough to neutralize the pathogen and prevent reinfection. It also produces large numbers of immune cells that can kill the virus.

Most tests that look for antibodies to the coronavirus have been flawed. But at least one team with a reliable test reported that most people, including those who were only mildly ill, make powerful antibodies. Data on immune cells has been slower to emerge, but a few studies suggest a robust response from immune cells as well.

What remains unknown is how long this immunity will last. There have been some reports of reinfection, but scientists have said that they are a result either of faulty testing, or of viral remnants that circulate long after the active infection has ended.

They are hopeful that based on other coronaviruses that cause the common cold, SARS or MERS, immunity to the new coronavirus might last at least a year, but it remains a mystery for now.

https://www.msn.com/en-gb/news/coronavirus/after-6-months-important-mysteries-about-coronavirus-endure/ar-BB14TR8v

Carly Fiorina's journey from secretary to CEO

The BBC's weekly The Boss series profiles different business leaders from around the world. This week we speak to Carly Fiorina, US business leader, political figure and philanthropist.

By Dave GordonBusiness reporter

• 1 June 2020

It should give hope to any young person striving to reach the top, knowing that Carly Fiorina started her business career as a humble secretary.

"I spent my time greeting visitors, answering phones, typing memos," she says. "But I was really committed to the job, arriving early, and leaving late."

Mrs Fiorina, 65, is looking back on her 21-year-old self, who in 1976 got her first full-time job at a small property company in Palo Alto, California.

From that modest start she went on to become the first female chief executive of a Fortune 50 company (the 50 largest firms in the US). This happened in 1999 when, aged 44, she was appointed to the top job at computer group Hewlett-Packard.

Image copyrightGETTY IMAGES

Image captionShe was in her mid-40s when she got the top job at HP

Fortune magazine subsequently named her the most powerful woman in US business five years in a row, with the publication declaring that "Carly Fiorina didn't just break the glass ceiling, she obliterated it".

However, her time at HP was not universally regarded as a success, with much criticism of her decision to merge the business with rival Compaq in 2001. And in 2005 she resigned after a disagreement with her fellow board members.

Mrs Fiorina subsequently entered the political arena, first as an adviser to the late John McCain's 2008 presidential campaign. McCain went on to lose the election to Barack Obama.

Eight years later, she herself ran to become the Republican Party candidate for the 2016 presidential election. She dropped out after nine months, due to low polling numbers, with Donald Trump going on to win both the candidacy and, of course, the presidency. She said at the time that she was "horrified" by Trump.

Image copyrightCARLY FIORINA

Image captionShe married her husband Frank in 1985

Born in 1954 in Austin, Texas, her family moved around a lot, due to her father's job. Her dad, Joseph Sneed, was a law professor who went on to become US deputy attorney general. Her mother was a painter.

She got a degree in philosophy and medieval history from Stanford University in California, before gaining a Master of Business Administration from the University of Maryland.

In 1980 she entered the technology sector when she joined US giant AT&T as a management trainee. Her rise at the company was meteoric. By 1990 she was the firm's first female vice president, and by 1995 she was a senior director at AT&T spinoff Lucent Technologies.

It was also while at AT&T that she met her husband Frank, and they were married in 1985.

Mrs Fiorina's success at the telecoms giant caught the attention of HP, who were looking for a fresh start after missing nine quarterly profit targets in a row. She was appointed to the top job at the company in July 1999.

"When I arrived at HP I purposely brought no-one new in at the beginning," she says. "I did that for a very explicit reason, which was to send a very clear message to the organisation that we could, and we would, figure out what the problem was, and we would fix it.

"[However], I was brought in by the board to transform the company. Those were the words they used."

Image copyrightGETTY IMAGES

Image captionMrs Fiorina went up against Donald Trump in the 2016 Republican presidential candidacy debates

Under Mrs Fiorina's leadership, costs were reduced, and eventually 30,000 jobs were removed from the combined 145,000 HP and Compaq workforce. A further 80,000 employees took pay cuts at a business which at its peak was worth $87bn (£71bn).

"Of course it is incredibly difficult to have to fire people, to have to lay people off," she says. "In that very difficult circumstance, the best I could do was to fully explain why.

"Why are we having to lay people off? Because if we don't, we will go out of business like many of our peers."

When the merger between HP and Compaq went ahead in 2002, it was the biggest ever in the technology sector at the time, and created the world's largest seller of personal computers.

Whether the merger was a success, however, is still hotly contested. Tech website ZDNet said in 2016 that HP and Compaq's coming together was "the worst merger ever". By contrast, the Huffington Post called it "the merger that worked".

What is certain is that the HP board were unhappy with the profits and share price of the combined business, and Mrs Fiorina was asked to resign in 2005. Her severance package was reportedly worth $21m.

Image copyrightCARLY FIORINA

Image captionShe now teaches charities leadership skills

"We did, in fact, restore a great company," she says. "[But] we had a dysfunctional board. It was dysfunctional when I arrived. It was dysfunctional when I left."

If leading HP wasn't enough of a battle, Mrs Fiorina jumped into politics for a decade from 2006. After working for John McCain, she went on to stand as the Republican candidate in the 2010 US Senate election in California, but lost out to the Democratic Party incumbent.

Mrs Fiorina then worked for the American Conservative Union, a right-wing lobbying organisation, before running to be the 2016 Republican presidential candidate. Looking back on this campaign, she says that "the process itself is insane".

She adds: "Meaning, when you think about the process the candidates go through, does it really help someone to be a better leader? Does it help us to decide a better leader? I don't think so.

"It is a really crazy process that goes on for far too long. It is far too driven by a media spectacle."

But with another US presidential election due to be held this autumn, what does she think of President Trump after his four years in office? She declines to comment.

More The Boss features:

• The man who sells 700 million sandwiches a year
• The man who bought 60,000 oil and gas wells
• The high-flying circus firm for pop and rock stars
• ‘After eight years on drugs, I run a million-dollar firm again'
• 'He said it was the stupidest idea he had seen'

While the worlds of politics and business can be tough, Mrs Fiorina's biggest fight came in 2009 when she was diagnosed with breast cancer, and subsequently required a double mastectomy.

She says the experience taught her a great deal. "While I hope to never go through cancer again, it was a very important part of my journey, and for that I'm grateful.

"I learned and grew so much during this time - learned about love and friendship, grew in my faith, and valued the kindness of strangers."

Image copyrightGETTY IMAGES

Image captionShe says that the US presidential campaign system is "crazy"

Technology firm boss Mihai Ivascu says that Mrs Fiorina is an "inspirational leader".

"She does not limit herself to what she is expected to do," says Mr Ivascu, who runs London-based M3 Holdings, and was included on a "Forbes 30 Under 30" list of leading young entrepreneurs. "And as she has said, leadership is about changing the status quo when it needs changing."

In recent years Mrs Fiorina, who lives with her husband in Washington DC, has dedicated most of her time to her charity work. This includes being the chair of Good360, which helps companies give their surplus merchandise to various charities, and running Unlocking Potential, which helps the bosses of charities improve their leadership skills.

Looking back on the start of her career, and her days as a secretary, she says: "I was going to be the best secretary out there. I had no idea where it would lead."

https://www.bbc.com/news/business-52820298